Introduction {#Sec1}
============

In ageing societies, the demand for joint arthroplasty repairing osteoarthritis in the proximal and distal femur continually increases. In Germany, a total of about 450,000 primary hip and knee arthroplasties due to arthrosis are performed every year \[[@CR1], [@CR2]\]. At the same time, there is a growing incidence of revision surgery after joint replacement. About 10,000 revisions of knee arthroplasties are performed, with an annual increase of about 10 % in Germany caused by the growing number of patients with long standing implants \[[@CR1]\]. Periprosthetic fractures (PPF) after knee arthroplasty occur in up to 2.5 % mounting up to 38 % after revision surgery \[[@CR3]--[@CR7]\].

The localization of PPF less frequently concerns the tibial component than the distal femur amounting up to 4 % of the cases. Felix showed in his work in 1997 that 19 % of these periprosthetic (PP) tibial fractures are brought forth intraoperatively during implantation of the prosthesis \[[@CR8]\].

Important complication rates of up to 41 % and revision rates of 29 % of cases are recently reported for surgical treatment of periprosthetic fractures \[[@CR9]--[@CR14]\].

Various reasons may eventually lead to postoperative problems:Bone quality is poor due to pre-existing osteoporosisStable fixation is difficult to achieve in areas with an intramedullary implantFracture healing is significantly delayed in aged patientsProsthesis loosening may facilitate the resulting fracture

Typical complications after internal fixation of periprosthetic fractures are the following:Loss of fixationNon-union and implant failureInfectionMalrotation and malunionLoosening of the prosthesis

Within this paper, we would like to present and discuss the modern strategies in classification, planning and treatment of periprosthetic fractures around knee arthroplasty.

Femur {#Sec2}
=====

To date, a variety of strategies for periprosthetic fracture fixation is described in the literature. The results of conventional non locking implants have generally been poor, with complication rates up to 53 % \[[@CR15]\]. Therefore, locking plates have become more commonly used in complicated osteoporotic fractures. Although fixation is tighter, the complication rates of this technique, nevertheless, remain high with up to 29 % failures \[[@CR9]--[@CR14]\]. The development of polyaxial screws and anatomic (periprosthetic) plates might be an advantage in improving fixation of PPF fixation \[[@CR16]--[@CR18]\].

In order to preserve the blood supply of the bone and to diminish local soft tissue complications, minimally invasive strategies are recommended by some authors even for periprosthetic fractures \[[@CR11], [@CR13], [@CR14]\]. Other authors still recommend the open approach \[[@CR9], [@CR10], [@CR12], [@CR16], [@CR19]\]. Although the revision rates in the papers describing minimally invasive techniques (0--12.5 %) seem to be lower than in studies on open approaches (7--29 % revisions), direct comparison is not possible, because fracture types, treatment strategies and implants are different.

Nevertheless, MIS strategies in PPF fixation remain challenging with respect to reduction and fixation techniques. Within this publication we will give additional tips on the less-invasive techniques in the fixation of PPF.

Diagnostics {#Sec3}
-----------

Standard anteroposterior and lateral views are the basis of fracture analysis and classification. Before classifying the fracture, the stability of the prosthesis should be assessed with respect to the patients' history before the trauma (a history of pain around the prosthesis may indicate previous loosening) and the situation evaluated on conventional X-ray. Typical signs of loosening like displacement of the shield from the distal femur or separation of cement may be detected. In ambiguous cases, a CT-scan may help find signs of loosening, particularly around the femoral component (Figs. [14](#Fig14){ref-type="fig"} and [15](#Fig15){ref-type="fig"}).

It is not always possible to establish a definitive diagnosis of a loose implant since, particularly, in a fracture situation, the loosening may be merely partial. Therefore, the surgeon should be prepared to eventually change to a revision prosthesis when an osteosynthesis was initially planned.

Sometimes, septic loosening may precede the PPF. Therefore, a microscopic (microbiological) analysis of the intraarticular fluid for white blood cells and bacteria is recommended in patients with clinical signs of infection.

Classification {#Sec4}
--------------

Periprosthetic fractures in the distal femur generally are classified by the Rorabeck classification \[[@CR20]\]. The Rorabeck classification discerns loose and unloose implants according to the level of displacement. Although other classifications considering the quality of the bone stock \[[@CR21]\] or the underlying implant (component with or without stem) have been published, their superiority still has to be proven.

The main advantage of the Rorabeck classification is its simplicity, but it is not always the best treatment guide, because other factors like the quality of the bone stock (e.g. osteoporosis), the underlying implant and the fracture type have to be considered when planning fracture fixation or replacement. In Figs. [7](#Fig7){ref-type="fig"} and [10](#Fig10){ref-type="fig"}, it is shown how fractures that are classified as Rorabeck type II can differ with respect to the type of prosthesis and type of fracture.

In order to plan the surgical approach, the Orthopaedic Trauma Association (OTA) classification of femur fractures (no. 32 and 33) may additionally be applied (see '[Surgical techniques](#Sec10){ref-type="sec"}').

### Rorabeck I {#Sec5}

Undisplaced fractures (less than 5 mm of displacement and less than 5° of angulation) around a stable fixed prosthesis in the distal femur are classified Rorabeck I.

Historically, periprosthetic Rorabeck I fractures have been treated conservatively. Some authors have reported good results in terms of fracture consolidation following conservative methods, but, in the majority of cases, their results don't report any data regarding knee function or systemic patient complications after the conservative treatment \[[@CR22], [@CR23]\].

In the 1970s to 1980s, the results of surgical management of these fractures with invasive techniques and conventional systems for osteosynthesis were, in many cases, inferior to conservative treatment. Therefore, conservative management was generally recommended for this type of fractures.

To date, both the improvement of implants (retrograde locked nails and locked plates) and the development of less invasive surgical techniques have substantially reduced surgical complication rates \[[@CR24]\].

Because of the high risk of secondary displacement and other complications, along with the need for early mobilisation, nonoperative treatment of periprosthetic fractures of the femur may not be favourable in most patients \[[@CR15]\] (see Figs. [1](#Fig1){ref-type="fig"} and [2](#Fig2){ref-type="fig"}).Fig. 1Anteroposterior (**a**) and lateral (**b**) view of a Rorabeck type 1 and OTA 33-A1 fracture around a resurfacing TKA; by Jordi ThomasFig. 2Postoperative anteroposterior (**a**) and lateral (**b**) view after mini open fixation with lag screws (through the plate) and a monoaxial locking plate (LISS Synthes®)

### Rorabeck II {#Sec6}

In this category, all fractures with a stable prosthesis but dislocated fragments are summarised. The treatment of choice is an open or closed reduction and internal fixation by plate or nail. Nevertheless, a revision prosthesis (see [Rorabeck III](#Sec7){ref-type="sec"}) can be a choice in selected cases of very low fractures and/or severe osteoporosis.

### Rorabeck III {#Sec7}

Fractures around a loose prosthesis with an undisplaced or displaced fracture situation are assigned to this category. Rorabeck III fractures require a prosthetic replacement with stable fixation of the stem in the central part of the femur.

Implants {#Sec8}
--------

Among a variety of possible implants, nails or plates are mostly used for the fixation of fractures with a stable prosthesis (Rorabeck I and II). In Rorabeck III fractures, the exchange to a prosthesis with a longer stem, providing proximal diaphyseal fixation, is the treatment of choice.

### Nails {#Sec9}

For intramedullary fixation of periprosthetic distal femur fractures, retrograde nails are used. Antegrade nails are not recommended, because distal fixation of these nails is not reliable.

Before planning a retrograde nail osteosynthesis, it has to be proven that the distal entry point between the condyles of a resurfacing total knee arthroplasty (TKA) is 'open' (Figs. [3](#Fig3){ref-type="fig"} and [4](#Fig4){ref-type="fig"}). In prosthesis with a box (e.g. posteriorly stabilised) or with a stem, a plate should be preferred. According to a recent analysis of the literature, there seems to be no difference in clinical outcome using a nail or a plate \[[@CR15]\].Fig. 3Anteroposterior (**a**) and lateral (**b**) view of a Rorabeck type 2 and OTA 32-B2 fracture around a monolateral TKA in a 77-year-old female patient; by Florian GebhardFig. 4Posoperative anteroposterior (**a**) and lateral (**b**) views after minimally invasive stabilisation with an intramedullary nail (DFN with twisted plate; Synthes®). The lateral view shows a mild retroversion of the distal fragment

Surgical technique {#Sec10}
------------------

For surgery, the patient is placed in the supine position on a radiolucent fracture table. It has to be considered that the knee should be flexed to 90° to allow the nail to pass behind the femoral shield. Reduction and fixation is performed after a mini open or minimally invasive reduction (see: '[Plates](#Sec11){ref-type="sec"}---[Surgical technique](#Sec12){ref-type="sec"}'). For retrograde nailing, the following tips could be respected:To allow optimal proximal fixation, the nail has to be long enough to pass the isthmus of the femoral intramedullary canal.Distal fixation of the nail is preferably done by locked bolts or a locked twisted plate (e.g. distal femur nail; Synthes®; Figs. [3](#Fig3){ref-type="fig"} and [4](#Fig4){ref-type="fig"}).Proximal locking should be performed after distal fixation of the nail. Only thereafter the jig can be removed and the knee extended. Before proximal locking, the optimal rotation of the femur has to be evaluated.

### Plates {#Sec11}

Plates may be applied in nearly all PPF situations. Because of the concomitant osteopenia or osteoporosis, locking plates should be applied. The authors suggest that at least four locked screws (eight cortices) should be set in both the diaphyseal and the metaphyseal area of the femur. If this cannot be achieved with all four screws because of an intramedullary prosthetic stem or box, additional techniques (like cerclage or a locking attachment plate; Synthes®) are needed.

#### Monoaxial locking plates {#d30e631}

Although monoaxial locking plates usually provide high primary stability, resisting high pull out forces, the application in situations with an intramedullary implant may be difficult. Therefore, additional devices like cerclage or additional plates (e.g. locking attachment plate; Synthes®) have to be applied at the level of the prosthesis to provide stable plate fixation (Figs. [5](#Fig5){ref-type="fig"} and [6](#Fig6){ref-type="fig"}).Fig. 5Anteroposterior (**a**) and lateral (**b**) view of a Rorabeck type 2 and OTA 32-A1 fracture around a resurfacing TKA and a proximal femur Nail (PFN A) in an 87-year-old female patient; by Florian GebhardFig. 6Postoperative anteroposterior (**a**) and lateral (**b**) views after open fixation with a monoaxial locking plate. For fixation around the intramedullary implant, a locking attachment plate (Synthes®) was applied

#### Polyaxial locking plates {#d30e672}

In order to pass by an intramedullary implant, polyaxial locking screws (e.g. NCB® - System; Zimmer®) might be of advantage. These implants offer the possibility of a polyaxial locking screw fixation in up to 15° in any direction to the plate level (full range of 30°). Some designs allow a reduction of the fragments in direction to the plate by the screws before they are locked. With the NCB®-System, angular stability is achieved by fixing the head of the screw with an additional cap turned into the plate (Figs. [7](#Fig7){ref-type="fig"}, [8](#Fig8){ref-type="fig"}, [9](#Fig9){ref-type="fig"}, [10](#Fig10){ref-type="fig"}, [11](#Fig11){ref-type="fig"}, [12](#Fig12){ref-type="fig"}, and [13](#Fig13){ref-type="fig"}).Fig. 7Anteroposterior (**a**) and lateral (**b**) view of a Rorabeck type 2 and OTA 33-A1 fracture of a hinged TKA in a 76-year-old female patient. Because of the stem and the box, there is only limited bone stock in the distal femur (**b**); by Steffen RuchholtzFig. 8Intraoperative pictures demonstrating the Mini open technique of open reduction with cerclage fixation (**a**) and stabilisation by a periprosthetic polyaxial locking plate (NCB PP; Zimmer®; **b**). Three distal locking screws were placed around the stem (**c**)Fig. 9**a, b** Follow-up X-ray pictures at 6 months after surgery. Because of the fixation with three distal screws, one additional cerclage was set around stem and plateFig. 10Anteroposterior (**a**) and lateral (**b**) view of an interprosthetic Rorabeck type 2 and OTA 33-A 3 in an 87-year-old man; by Steffen RuchholtzFig. 11Intraoperative picture of a minimally invasive insertion of a periprosthetic plate (NCB PP)Fig. 12Intraoperative X-ray pictures demonstrating the minimally invasive technique of closed reduction with temporary proximal plate fixation (**a**) and reduction of the fragments by the screws through the plate (**b**)Fig. 13Postoperative anteroposterior (**a**) and lateral (**b**) views. The plate was selected to be long enough to over lap the tip of the THA in order to prevent stress raising at the 'inter implant' region. **c** shows the dimension of the needed incisions

Specially designed periprosthetic plates (NCB-PP®; Zimmer®) have a broader metaphyseal area augmenting the possibilities in PPF fixation especially around uncemented implants (Fig. [8c](#Fig8){ref-type="fig"})

### Surgical technique {#Sec12}

Plating may be performed in different techniques of reduction and fixation. Reduction can be achieved either directly (forceps and lag screw/cerclage) in two-part long spiral fractures (OTA Type 32 or 33-A1) or by bridging the fracture zone when direct reduction cannot be achieved (e.g. multi-fragmented fractures). These principles should be respected independently from the selected approach (see below).

Although 'open' techniques allow for direct visualisation of the fracture, impairment of the local bony perfusion after manipulation of the soft tissue is of some concern. Since fracture healing is already impaired in geriatric patients, especially when there is an intramedullary implant, soft tissue-preserving strategies like a 'mini open' or a 'minimally invasive' technique might be of certain advantage.

The 'open' technique is a common procedure for PPF fixation. Using a lateral subvastus approach after ligation of the perforator vessels, the bone is exposed. The incision has to be long enough to allow for the application of a plate that is sufficiently long (Figs. [5](#Fig5){ref-type="fig"} and [6](#Fig6){ref-type="fig"}). Bony fragments have to be managed with care to avoid impairing the soft tissue that provides the local blood supply.

The 'mini open' technique is an alternative in two-part spiral fractures classified as OTA (Orthopeadic Trauma Associoation) type 32-A1 or 33-A1. For this technique, an incision at the level of the plate insertion is made, sufficiently long to expose the fracture region. The two fragments are reduced by the help of a forceps until an optimal contact with anatomical alignment of axis and rotation is achieved. The reduction forceps is then replaced by cerclages or a lag screw (Figs. [7](#Fig7){ref-type="fig"}, [8](#Fig8){ref-type="fig"}, and [9](#Fig9){ref-type="fig"}).

After this step, the plate is inserted and temporarily fixed percutaneously with K-wires proximally and distally. Before the screws are set, a lateral view to control the plate position is performed by use of the intensifier.

The screws in the diaphyseal region are inserted percutaneously. The femur is not exposed in the diaphyseal area.

The concept of the 'minimally invasive' technique is a totally closed reduction. Reduction is achieved by either ligamentotaxis and/or the application of the plate as a template. Therefore, maintaining the correct alignment by axial traction throughout the whole procedure is of essential priority. Traction can be exerted throughout the procedure by the assistant surgeon. After closed reduction, the plate is inserted on the level of the prosthesis after a short 3- to 4-cm incision (Fig. [11](#Fig11){ref-type="fig"}). After this step, the plate is temporarily fixed with K-wires proximally and distally, length must be restored at this point (Fig. [12](#Fig12){ref-type="fig"}). Before the screws are set, a lateral view to control the plate position is performed with the intensifier.

By setting the shaft screws, the plate can be used as reduction tool (Fig. [12](#Fig12){ref-type="fig"}) if no primary locking screws are applied. Locked screws can be set when the plate is running parallel to the diaphysis.

Before the screws are placed in the metaphyseal area, the axis has to be controlled. Some institutions use the 'cable-technique' where the straightened cable of the electric coagulation device simulates the mechanical axis. Correct reduction is achieved when the intensifier proves that the straightened cable is projected on the centres of hip, knee and ankle. Thereafter, the screws are set in the metaphyseal region (Fig. [13](#Fig13){ref-type="fig"}).

### Revision prosthesis {#Sec13}

n patients with prosthetic loosening, the whole implant has to be exchanged to revision prosthesis with diaphyseal fixation (Figs. [14](#Fig14){ref-type="fig"} and [15](#Fig15){ref-type="fig"}). For revision, mostly modular systems are applied that are implanted by a lateral or standard parapatellar incision (in short distal fragments). In general, a hinged prosthesis has to be implanted because of the involvement or the resection of the collateral ligaments. Therefore, the whole implant including the tibial component has to be exchanged (Fig. [15](#Fig15){ref-type="fig"}) in most cases. In patients with severe bone loss around the implant, partial replacement of the distal femur (e.g. resection prosthesis) may be considered.Fig. 14Preoperative X-ray (**a**) and CT (**b**) view of a partially loose PPF type Rorabeck III, OTA 33 C1; by Steffen RuchholtzFig. 15**a, b** Postoperative x-ray after implantation of a hinged revision TKA

Tibia {#Sec14}
=====

Periprosthetic fractures around the tibial component are rare, with an incidence of \<4 %.

Diagnostics {#Sec15}
-----------

Analogous to fractures around the femoral component, the stability of the prosthesis is evaluated with respect to the patients' history before trauma and X-ray diagnostics. Typical signs of loosening like displacement of the shield from the distal femur or separation of cement may be seen on x-ray in cases of prosthesis loosening. Nevertheless, in difficult cases, a CT-scan may be helpful in order to detect loosening around the tibial component.

Classification {#Sec16}
--------------

Felix et al. have suggested a classification based on a study on 102 tibial fractures around total knee implants \[[@CR8]\].Type 1:Fracture partially involving the tibial headType 2:Fracture involving the whole tibial head around the implantType 3:Fracture lying below the distal part of tibial componentType 4:Fracture with an isolated involvement of the tuberosity

The four fracture types in the classification are combined with a suffix:A---stable prosthesisB---loose prosthesisC---intraoperative fracture

Conservative treatment {#Sec17}
----------------------

Fractures without displacement around a stable prosthesis may be treated conservatively. This strategy is recommended for most undisplaced partial fractures of the tibial head (Type 1A and 1C fracture). Fractures involving the whole tibial head may be treated conservatively, particularly when they occur intraoperatively during the implantation of the prosthesis and do not show any displacement in neither of the planes on X-ray (Type 2A and 2C fracture). Conservative treatment includes cast fixation and non-weight bearing of the knee for 6 weeks.

Surgical treatment {#Sec18}
------------------

Surgical revision is recommended in all displaced tibial PPFs. Even undisplaced fractures below the prosthetic component (Type 3A or 3C) should be considered for internal fixation because of a high risk for pseudarthrosis (Figs. [16](#Fig16){ref-type="fig"} and [17](#Fig17){ref-type="fig"}).Fig. 16**a, b** Preoperative X-ray of a periprosthetic fracture around the tibial component of a TKA type Felix 3A; by Morten Schultz LarsenFig. 17**a, b** Postoperative X-ray 6 months after stabilisation with a locking plate (LISS; Synthes®)

All types of fractures that are accompanied by a loosening of the tibial component should be treated by a revision of the implant.

### Plates {#Sec19}

For fractures with a stable implant (types 2A and C; types 3A and C), monoaxial or polyaxial locking plates are the treatments of choice. They can be applied either in open or in a less invasive technique. Because of the relatively thin soft tissue layer, percutaneous fixation of the distal plate to the diaphysis after 'mini open' or 'minimally invasive' reduction is easy to achieve and allows a maximum preservation of the local blood supply.

The risk of soft tissue complication, including deep infection is much higher than on the distal femur, and the surgeon must have this in mind when planning the treatment. Fractures of the tuberosity (type 4) may be fixed either by isolated lag screws (big fragments) or by plates.

### Revision prosthesis {#Sec20}

In a loose prosthesis (fractures with a suffix B), the whole implant has to be exchanged to revision prosthesis with diaphyseal fixation. For revision, modular systems are applied that are implanted by a lateral or standard parapatellar incision (in short proximal fragments). In general, a hinged prosthesis should be implanted because of the involvement or the resection of the collateral ligaments. Therefore, the whole implant including the femoral component has to be exchanged.

In cases with severe bone loss around the implant, partial replacement of the proximal tibia (e.g. tumour prosthesis) should be considered.

Postoperative care {#Sec21}
==================

It is of great importance for the aged patient to be mobilised out of bed early in order to prevent the health problems of immobilisation. Nevertheless, primary stability that allows full weight bearing cannot always be achieved by plating or nailing. In most of the cases, partial weight bearing is recommended using the aid of frames during the first 6 weeks after surgery.

In well-fixed revision prostheses with a cemented stem, early full weight bearing might be allowed. In uncemented revision stems, care must be taken out within the first 6 weeks after the operation. After consolidation of the soft tissue, all PPF surgery patients should be treated with continuous passive motion of the knee.

Special Issue: Periprosthetic Fracture Treatment

Open Access {#d30e1015}
===========

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.


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OPINION

Somebody say something

In this season of motion picture accolades, Alabama’s “best actor” award goes to Chief Justice Roy Moore, starring in a continuing saga of abuse of power. However, Moore’s “performance” is facilitated by the neglect manifest in the failure of other entities to address his professional lunacy.

The Cast. The cast includes present and former justices of the Alabama Supreme Court. As Chief Justice, Moore is the administrative head of Alabama’s court system, but he, like each of the Associate Justices of the Supreme Court, has but one vote in the cases they decide. His individual, personal view of the law is not binding on any other Alabama judge or lawyer. Since the justices are independently elected to office, Moore is not their “supervisor.”

Associate Justices have an affirmative professional duty to reject (1) Moore’s extrajudicial positions on a legal issue pending before the Court, (2) his continued affiliation with a Foundation (chaired by his wife, Kayla) that is a litigant in the Supreme Court on an issue upon which Moore has publicly expressed an opinion, and (3) his directive to probate judges to repudiate a U.S. Supreme Court ruling.

How? By exercising their power under Section 12-5-20 of the Code of Alabama, which grants them “the power and authority to review, countermand, overrule, modify or amend any administrative decision by either the Chief Justice or the Administrative Director of Court.” Thus, the justices may lawfully rescind Moore’s administrative directive to probate judges to refuse to issue marriage licenses to same-sex couples. Surely they must understand the Supremacy Clause in the U.S. Constitution. Surely they must place the integrity and reputation of the court above political fealty to a colleague. And yet, the justices are silent.

The Producer. That would be the Judicial Inquiry Commission, which has neglected its duty for 12 months. The pending complaint against Moore alleges wrongdoing associated with specific acts. Moore does not dispute the facts. JIC’s sole responsibility is to determine whether the allegations are sufficient to support a recommendation to the Court of the Judiciary. That is not a 12-month undertaking. And yet, JIC is silent.

The Director. The Court of the Judiciary controls the action. In March 2013, citing “serious violations of judicial ethics”, the Court of the Judiciary publicly reprimanded and censured a district judge in Walker County for essentially the same violations alleged in the Moore complaint. The Court found that he violated specific provisions of the Canons of Judicial Ethics which govern the professional conduct of Alabama’s judges. It took 45 days to conclude the complaint. And yet, the Court of the Judiciary is silent.

The Theaters. The Alabama State Bar is the parent organization of the theaters (lawyers) where the patrons (the public) are viewing Moore’s movie. The Bar enjoys the legislative privilege of managing and policing lawyers and is specifically charged in Section 34-3-43 (a) (7) of the Code of Alabama to “do such things as in its judgment may tend to improve the educational and ethical standing of bench and bar.” The State Bar also administers the Alabama Rules of Professional Conduct which define a lawyer’s obligations to the judicial system, to the public, and to the profession. Rule 8.4 assigns “professional misconduct” to any lawyer who (1) engages in “conduct that is prejudicial to the administration of justice,” (2) “knowingly assist[s] a judge or judicial officer in conduct that is a violation of applicable ... law, or (3) engages in “any other conduct that adversely reflects on his fitness to practice law.”
While the state bar does not discipline judges, its duty to fulfill the aforementioned responsibilities justifies condemnation of Roy Moore’s conduct from its leaders, former presidents, and members. Protection of the public is a paramount duty of the state bar and the 67 county bars. Their silent acceptance of willfully unprofessional and unlawful conduct by the state’s highest-ranking judge is an abandonment of their duty to serve the public. And yet, the state and county bars are silent.

We have seen this movie before. In the 1960s, its star was an executive, not a judicial, demagogue. Back then, as now, the cast, producer, director and theaters were silent. Today – 50 years later – his performance is still an embarrassment to Alabama.

Somebody say something.

Vanzetta Penn McPherson is a retired U.S. magistrate judge for the Middle District of Alabama. Send email to mcphersonscribe@knology.net.


BRAINTREE, Mass. -- For the first time since being drafted by the New England Patriots in 2010, punter Zoltan Mesko will face competition for his job.

Former Louisiana Tech punter Ryan Allen, who went undrafted last week, tweeted on Saturday that he will be joining the Patriots.

"Ready to take my talents to New England!" Allen tweeted. "Excited to compete and be a part of a first class organization! ... Cannot wait to grind toward success as a Patriot!"

Last season, Allen became the first back-to-back winner of the Ray Guy Award, given annually since 2000 to the best punter in college football.

Meanwhile, Mesko enters the final year of his rookie contract. Statistically, he saw a slight drop in his gross punting average last season (43.1 yards per punt after posting a 46.5 mark in 2011), although that may have been offset in part by a career-high 28 punts downed inside the 20-yard line.

On Wednesday, Mesko told ESPNBoston.com that he is ready to embrace the competition.

"I'll control what I can control," he said. "It's healthy competition and that's what got us here in the first place. So I welcome whatever the coaches feel is best for me."

This is the first time in his NFL career that Mesko, who was selected in the fifth round out of Michigan in 2010, could enter training camp battling with another punter on the roster.

"If Ryan has any questions, I'll be happy to answer them," Mesko said. "Get him caught up to things."

Mesko and special teams captain Matthew Slater were in Braintree on Wednesday, speaking to students at Ross Elementary School about the importance of physical activity.

"What better way to form your habits as a kid when you're a sponge and will absorb things from your role models?" Mesko said.


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Some people think that cats have an independent nature that can stand alone without a human companion. This perception might be true and applicable to those felines who are just roaming the streets and seemed no one or home to turn to. But, if you own one or have a...


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Seamus Coffey - Lecturer in Economics, UCC

According to this latest daft.ie report, the first quarter of 2012 provided the
least change in the property market since the middle of 2007. Asking prices
continued to fall, but the drop of 1.7% is the smallest quarterly drop since
the market collapse began in earnest in 2008. Meanwhile, in the rental sector,
stabilisation has been present for almost two years and nominal rents at the
start of 2012 are no different than they were at the start of 2010.

Measuring the fall

Measuring prices in the Irish property market continues to be an art rather than
a science. Using mortgage market data, the Central Statistics Office reports that
house prices fell by over 4% in the first two months of the year. When looking at
falls from the peak, though, a different picture emerges. The daft.ie report shows
a total fall of 53%, compared to 49% in the CSO index. The scope for divergence
in estimates of falls from the peak will hopefully be put to an end when a National
House Price Register is launched later this year.

House prices are always and everywhere a function of bank lending, but they do
have a fundamental value to which they must eventually return. This can be given
as a ratio to household income or, more usually, annual rents. A good guide is
that house prices should be somewhere between 12 and 15 times the annual rent
that a property can generate. This is a range that should never be ignored but
often is.

A market that has normal level of activity would be near the top of this range
but a malfunctioning market will be towards the lower figure and possibly even
below it. And Ireland does not have a properly function property market.

A depressed market

Data from the Irish Banking Federation show that there are fewer than 4,000 mortgages
being drawn down each quarter, with around half of these going to first-time buyers
and a further third to mover-purchasers. The remainder is largely accounted for by
re-mortgages and top-ups. The residential investment borrower has virtually disappeared.

Anecdotal reports suggest that around 30% of all purchases are by cash buyers. This
cannot be independently verified but a figure close to it would suggest there are
around 4,000 residential property transactions a quarter. Ireland has a housing
stock of around 2 million units. An annual turnover rate of less than 1% is indicative
of a market that continues to be distressed.

The stock of properties for sale on Daft.ie in March 2012 was 54,000, which is
the lowest level in four years. This could be because properties on the market
are selling quicker or because the number of properties being offered for sale
is declining. The speed at which properties on Daft.ie found a buyer did increase
slightly in the first quarter but two-thirds of properties remain on the market
for four months or longer before finding a buyer.

Thinking like investors

The average asking price for the first quarter of 2012 was €176,000. In order to
justify that price using the above range, the monthly rent should be somewhere
between €1,000 and €1,250. Averages do not provide the necessary insight and this
must be done on a town-by-town or even a street-by-street basis.

For example, a three-bed house in Cork City had an average asking price of €189,000
in the first quarter. The average asking rent for a similar property is €850 a month.
The annual rent is still more than 18 times the asking price. At a ratio of 15 times
annual rent, a monthly rent of €850 should equate to a price of around €155,000. By
this metric, asking prices for three-bed houses in Cork City are still around
one-sixth over-valued. This can be repeated right around the country. With the
inability and unwillingness of banks in Ireland to issue loans a fall below this
level is all but guaranteed.

The importance of lending

Just as the banks are almost certain to cause an undershooting of property prices
relative to their fundamental value they must accept the responsibility for the
market bubble that peaked almost five years ago. The banks based their lending
model on the prices that people were willing to pay for properties, but seemed
to ignore the fact that the price someone was willing to pay was based on how much
a bank was willing to lend to them.

A house in a particular estate may have sold for €350,000 because one bank was
willing to lend one purchaser the money for such a transaction. The other banks
provided similar mortgages to other buyers on the basis that the first transaction
provided the "market value".

The price reflects the amount of money that someone is willing to pay for a good.
Value reflects the benefits that a good can offer. In most cases, these are the
same but this does not have hold. Residential property provides accommodation
service. As a result of the madness of the boom, we now have thousands of households
paying a price for accommodation far in excess of the value they are receiving.

This reality must be addressed and the burden of the mortgage debt is largely a
function of the actions of the banks so they must offer what ever forbearance is
necessary to assist households. The banks must also realise that there are
thousands of homeowners who will never be able to repay the huge loans they
issued to them. It is very difficult to gauge the number of unsustainable
residential mortgages that need to be ended but it could be anywhere between
15,000 and 30,000. These are households who are in deep mortgage arrears and
negative equity and have little prospects of recovery.

The banks must face up to losses that exist on these loans. The homeowners must
accept that they will never be in a position to repay the loan and that by
surrendering the property they will be able to make a fresh start. Households
with unsustainable mortgages must be allowed to do so.

The recovery in the housing market will not be when prices start to rise; the
recovery will be when activity starts to rise. With our ailing banks still in
no position to lend and the many problems created by the bubble still outstanding
there is no sign that this is about to change.


Aledmys Diaz fouls a ball off, but it bounces off the dirt and back up into his face and forces him out of the game in the 9th inning


Facing domestic heat over the increasing oil prices, India is reportedly in talks with China for setting up a body that could negotiate better terms with sellers.

According to a PTI report, India discussed with China the possibility of forming an ‘oil buyers club’ for negotiating better terms with oil sellers as well as getting more US crude oil to Asia to cut dominance of the oil producers’ cartel OPEC.

Related Stories

The move comes after a realisation in government circles that OPEC’s actions were playing havoc with oil prices.

The idea was actually floated by Oil Minister Dharmendra Pradhan’s at the International Energy Forum (IEF) meeting in New Delhi in April this year.

As a follow up, Indian Oil Corp (IOC) Chairman Sanjiv Singh travelled to Beijing this month to meet Wang Yilin, Chairman of China National Petroleum Corp (CNPC), PTI quoted a top source as saying.

On discussion table was debottlenecking infrastructure to facilitate more US crude oil comes to Asia so as to cut the dominance of Organization of the Petroleum Exporting Countries (OPEC), which supplies about 60 per cent of India’s oil needs.

Production cuts by OPEC have led to international oil prices hitting a four year high last month that forced a Rs 3.8 per litre hike in petrol and Rs 3.38 a litre increase in diesel prices. Rates started to cool towards month end and retail prices have been cut thereafter.

In a throwback to 2005 when the then oil minister Mani Shankar Aiyar had proposed an alliance of the oil consuming nations, Pradhan wants to form an oil buyers club with China, Japan and South Korea to take up issues like premium being charged from Asian buyers.

At the IEF meeting, India and China agreed to join hands to have a collective bargaining power against cartelisation of oil producers. Singh’s visit was to take this forward with concrete proposals for cooperation, the source said.

So far, India has not been able to bargain better rates from the Gulf-based producers of the oil cartel, OPEC. Instead of getting a discount for bulk purchases, West Asian producers, such as Saudi Arabia, charge a so-called ‘Asian Premium’ for shipments to Asian buyers, including India and Japan, as opposed to Europe. According to Prof Yoshiki Ogawa of Japan, the Asian Premium annually costs somewhere around USD 5-10 billion for Asian importers.

The source said possibilities of joint sourcing of oil as well as combined bargaining to bring down Asian premium was discussed. Similar collaboration will be proposed to Japan and Korea as well.

With CNPC or its affiliates selling in the overseas market a large portion of oil produced from fields it owns in third countries, India expressed interest in buying the Chinese firm’s equity oil directly, the source said.

India is the world’s third-largest oil importer after China and the US. Japan is the fourth largest importer and South Korea is right behind it. The four nations account for over a third of the oil imports in the world.

“Why should biggest consumers pay more. Why should these countries pay more in name of Asian premium,” Pradhan had said in April. “All the four major Asian economies should come together. And India will try to create a network for that within the four countries.”

He had stated that like producers have a say in pricing and supply, consumers should also get a say.

This is India’s third attempt to unite major Asian energy importers to beat the producers’ cartel.

The then oil minister Aiyar had in 2005 hosted two ministerial roundtables to impress upon the need for a reasonable oil pricing and getting rid of discriminatory Asian Premium—the first involved major Asian consumers such as China, Japan and South Korea and the other roped in alternative oil producers of North and Central Asia.

Aiyar proposed a common front on oil to China’s National Development and Reforms Commission vice-chairman Zhang Xiaoqing. That proposal resulted in a memorandum of understanding in 2006 but it was lost in the complexities of bilateral ties.

Another attempt for joint energy sourcing with Japan was made towards the end of the UPA government when M Veerappa Moily was the oil minister. It, too, failed to see the light of day.

At the 16th IEF ministerial meet in April this year, India and China, which together accounted for 17 per cent of world oil consumption last year, agreed to look for ways to leverage the combined size of their imports for a better bargain from West Asian crude producers.

By 2023, oil demand will hit 104.7 million barrels per day, up 6.9 million bpd in 2017, according to the International Energy Agency. “As has been the case for some years, China and India together will contribute nearly 50 per cent of global oil demand,” the agency had said in a report.


Q:

How to change two properties in two different classes on hover?

I have made two classes in a SVG-file to decide the fill color of many many different shapes. The different shapes are grouped and now I want them to change differently on hover. On hover I want all the fill in class "test1" (that are inside the groupe) to change to e.g. #000000 and to set the opacity in the class "test2" to 0.8.
<style type="text/css" >
    .test1 { fill:  #006600;}
    .test2 { fill:  #0000FF; opacity: 0.3;}
    g:hover { ????? }
</style>

Any leads?

A:

Assuming a markup such as...
<g>
  <rect class="test1" ... />
  <rect class="test1" ... />
  <rect class="test2" ... />
  <rect class="test2" ... />
</g>

Your CSS would be...
.test1 { fill:  #006600;}
.test2 { fill:  #0000FF; opacity: 0.3;}
g:hover .test1 { fill: #000; }
g:hover .test2 { opacity: 0.8; }


// Copyright (c) Lex Li. All rights reserved.
//
// Licensed under the MIT license. See LICENSE file in the project root for full license information.

namespace Microsoft.Web.Administration
{
    public enum PipelineState
    {
        Unknown = 0,
        BeginRequest = 1,
        AuthenticateRequest = 2,
        AuthorizeRequest = 4,
        ResolveRequestCache = 8,
        MapRequestHandler = 16,
        AcquireRequestState = 32,
        PreExecuteRequestHandler = 64,
        ExecuteRequestHAndler = 128,
        ReleaseRequestState = 256,
        UpdateRequestCache = 512,
        LogRequest = 1024,
        EndRequest = 2048,
        SendResponse = 536870912
    }
}


Load characteristics following transfemoral amputation in individuals fitted with bone-anchored prostheses: a scoping review protocol.
The main purpose of this scoping review is to characterize loading information applied on the residuum of individuals with transfemoral amputation fitted with an osseointegrated fixation for bone-anchored prostheses.The objectives of this scoping review are: i) to map the scope of loading variables, and ii) to report the range of magnitude of loads that has been directly measured using a portable kinetic recording apparatus fitted at the distal end of the residuum during rehabilitation exercises, standardized and unscripted activities of daily living, and adverse events.The specific review questions are.


Munenori Kawasaki doesn't always give English interviews, but when he does, they are among the best in history.

First, let's set the stage. Sunday started off as just an ordinary day. Baseball games were being played, and the struggling Toronto Blue Jays trailed the Baltimore Orioles, 5-2, heading into the bottom of the ninth.

But the Jays rallied for four runs off closer Jim Johnson, with the ball-of-energy shortstop providing the game-winning two-run double.

Mark De Rosa, who scored the winning run, began the postgame interview but quickly stepped aside so Kawasaki could have his awesome moment in the spotlight.

He didn't disappoint:

"My name is Munenori Kawasaki. I am from Japan. I am Japanese!"

After those spectacular first words, he went on to thank his teammates for giving him the opportunity to secure the clutch hit. Shortly after, he was nailed with the shaving-cream pie and Gatorade bath.

Let me just say this.

I am (sadly) a Seattle Mariners fan. I was sad when Ken Griffey Jr., Randy Johnson and Alex Rodriguez left. I've been sad about this team pretty much my entire existence.

But when the M's let go of Kawasaki, I shed more than a single tear.

He isn't going to tear the cover off the ball, although he now has his average up to .247 after Sunday's 3-for-5 day, but he is always this excited. Always playing with passion, always giving everyone high fives.

As we now know, he gives some of the most entertaining interviews of all time.

It's always apparent that Kawasaki simply loves the game of baseball and is ecstatic to be playing it for a living, and with moments like these, he can put a smile on anyone's face.

Kawasaki wins—at everything. Forever.

Follow @t_keen


Q:

Printing Glossary entries without ever referencing them in your work

I am yet to create my list of abbreviations and symbols using the package Glossary. Since i am done with my thesis, i wont be referencing the glossary entries in the text where i used them. Is it possible that with the glossary package i can still print my abbreviations without ever referencing them?

A:

Is there a really good reasen why you want to use the obsolete package glossary? If not, I would suggest switching to the newer package glossaries. Using this package you can add entries, that were never referenced in you text, to your list of abbreviations using the following command.
\glsadd{}


Warren Buffett is Buying Stocks

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The NY Times just ran an interesting Op-Ed piece from Warren Buffett. In it, he talked about his current view of the market, and how he’s been handling his personal investments:

Iâ€™ve been buying American stocks. This is my personal account Iâ€™m talking about, in which I previously owned nothing but United States government bonds… If prices keep looking attractive, my non-Berkshire net worth will soon be 100 percent in United States equities.

So… Why is he wading into stocks given the current market turmoil?

A simple rule dictates my buying: Be fearful when others are greedy, and be greedy when others are fearful. And most certainly, fear is now widespread, gripping even seasoned investors. To be sure, investors are right to be wary of highly leveraged entities or businesses in weak competitive positions. But fears regarding the long-term prosperity of the nationâ€™s many sound companies make no sense.

He goes on to argue that:

I canâ€™t predict the short-term movements of the stock market. I havenâ€™t the faintest idea as to whether stocks will be higher or lower a month â€” or a year â€” from now. What is likely, however, is that the market will move higher, perhaps substantially so, well before either sentiment or the economy turns up. So if you wait for the robins, spring will be over.

What about holding cash for safety?

Today people who hold cash equivalents feel comfortable. They shouldnâ€™t. They have opted for a terrible long-term asset, one that pays virtually nothing and is certain to depreciate in value. Indeed, the policies that government will follow in its efforts to alleviate the current crisis will probably prove inflationary and therefore accelerate declines in the real value of cash accounts.

Interesting thoughts from a guy who knows. I tend to agree with him on all accounts, though I admittedly didn’t have the foresight to move into a 100% bond position like he did. Anyway, I highly recommend clicking through and reading the full article.

6 Responses to “Warren Buffett is Buying Stocks”

True cheap doesnt always equal growth, but I do think that VALUE=GROWTH and that Buffett is not saying that we are headed back to growth but a return to norm. This is almost the invert as 1999-2000 when everyone said its different this time. Stocks are simply oversold from a historical perspective.

Cheap doesn’t equal growth, but apparently Buffett believes the US economy is headed for growth. Few has predicted the extent of this crash, and I believe fewer can predict how long it will take to get out of this position. The past has shown the rise after such massive selloffs to be substantially longer, especially if there are no pockets of growth.

I agree. Don’t forget that he predicted both the internet bubble and the current one:
In 1999 when everyone was busy buying internet stocks he said:
“After a heady experience of that kind, normally sensible people drift into behavior akin to that of Cinderella at the ball. They know that overstaying the festivities… will eventually bring on pumpkins and mice”.

At that time everyone thought he was an old fool who doesn’t understand the “new economy”. He turned out to be right – we got pumpkins and mice….

Then in 2003:
“We’ve found it hard to find significantly undervalued stocks. The shortage of attractively-priced stocks in which we can put large sums doesn’t bother us. Our capital is underutilised now, but that will happen periodically. It’s a painful condition to be in but not as painful as doing something stupid.”

Also in 2003, about mortgage-backed securities and derivatives: â€œfinancial weapons of mass destruction, carrying dangers that, while now latent, are potentially lethal.â€

In both cases he turned out to be right. Listening to him in 1999 and 2003 would’ve saved many of us a whole lot of money.

Warren Buffet is the King Solomon of our day. I think that his philosophies should be defined and broadcast to anyone that would like to listen. I am not surprised at all that he is investing so heavily in stocks. If he had the time, I’m sure he would be heavily involved in local real estate markets too.

I think more investors should follow in Buffet’s foot steps. Everything is at a astronomical level right now and there are a lot of great buying opportunities that present themselves. Most people think a recession is a bad thing, but if you are a true investor, you will beg to differ.

Disclaimer:
Because rates and offers from advertisers shown on this website change frequently, please visit referenced sites for current information. This website may be compensated by companies mentioned through advertising, affiliate programs or otherwise.

Advertiser Disclosure: Many of the savings offers
appearing on this site are from advertisers from which this website receives compensation for being listed here.
This compensation may impact how and where products appear on this site (including, for example, the order in which they appear). These offers do not represent all deposit accounts available.

Editorial Disclosure: This content is not provided or commissioned by the bank advertiser. Opinions expressed here are author's alone, not those of the bank advertiser, and have not been reviewed, approved or otherwise endorsed by the bank advertiser. This site may be compensated through the bank advertiser Affiliate Program.

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NFL: Tight Ends with the Most Postseason Receiving Yards

Jason Witten? Not yet. This weekend, though, he’ll crack the list of top 20 tight ends with the most postseason receiving yards.

Witten – one of the better offensive tight ends to ever hit the grid, one of only four TE’s with over 10,000 career receiving yards and a possible Hall of Famer – has only been in six playoff games in his 12-year career. Tony Romo‘s Dallas Cowboys have been up and down during the regular season and mostly down in the postseason. Witten’s got 356 yards, just four off the pace.


Excessive load shedding hits Naudero hard

Naudero: Excessive electricity load shedding than the announced schedule has crippled daily life and trade activities of Naudero.
The local Sepco authorities had announced daily outage of 8-hours but they are carrying out 16-hours load shedding daily.
As per announced timings they have to close supply from 3.45 am to 5.45 am, ...


Ethanol sensitivity of recombinant human N-methyl-D-aspartate receptors.
In this study, the ethanol sensitivity of human N-methyl-D-aspartate (NMDA) receptors stably expressed in L(tk-) cells, or transiently expressed in HEK 293 cells and Xenopus oocytes was determined. NMDA receptor function was measured using fura-2 calcium imaging for L(tk-) cells, whole cell voltage-clamp for HEK 293 cells, and two-electrode voltage clamp for oocytes. Ethanol inhibited NMDA receptor function in all three expression system, but was less potent for receptors expressed in L(tk-) cells. NMDA receptors composed of NR1a/2B subunits were inhibited to a greater extent by ethanol than NR1a/2A receptors when expressed in L(tk-) cells and HEK 293 cells, but not in oocytes. These results suggest that the method of receptor expression and assay system used may influence the degree of ethanol inhibition of recombinant NMDA receptors.


Momo is so cute in this video with her anime maid clothes and the pink hair and freckles. If you like anime or hentai, it's a pretty neat interpretation in live action. It's fun, it's got a story, and the sex is wonderful. If you like cute and sexy with real b/g action, this is the one to get.

D wakes up oneday to find his childhood friend Momo dressed as a maid. Turns out she was sent by his family member to take care of him for the week. There is lots of comic anime-style beatings and of course hentai style sex - but without the censorship!
Outfit: Pink Loli Maid
This video was based off the hentai "My TsunTsun Maid" as an experiment for a live action hentai


1. Field of the Invention
The invention relates to a steerable ground drilling device, which comprises a body destined to be attached to a flexible pipe, a rotatable head which is mounted on the front extremity of the body and is provided with at least one spraying device to which fluid under pressure can be supplied through a pipe which extends through the head and the body and means for rotating the head.
2. Discussion of the Related Art
Such steerable ground drilling devices are especially utilized for making for tunnels in the ground into which the laying of so-called public utilities, such as cables and such and the like, is accomplished.
The steering of the ground drilling device can occur in various ways.
It is known to attach the head of the steerable ground drilling device to the body by means of a ball and socket joint, such that it can be fitted in relation to the body.
It is also known to provide the head with a guidable spraying device and to alter the spraying direction of the spraying device if required.
In yet another known ground drilling device the spraying device or a hammer drill is directed asymmetrically in relation to the axis of the body.
With continual rotation, the drilling device will move straight forward. With a stationary head the spraying is asymmetric and the drilling device will alter direction if it is pressed further rotatingly or hammered rotatingly.
With all these ground drilling devices the head must be stationary with alteration of direction.
Ground drilling devices are known whereby the head can rotating, even during the alteration of direction. In this way ground drilling devices are known whereby laterally directed spraying devices are provided in the body in order during the alteration of direction, to press the body away from the wall of the already formed opening.
All these known ground drilling devices are, however, relatively complicated and the steering of them is not easy.


Background {#Sec1}
==========

Spontaneous intracerebral hemorrhage (ICH), especially in patients with severe coma, has a high mortality and disability rate. The pathophysiology of ICH is incompletely understood; there is general agreement that the acute formation of a parenchymal hematoma produces tissue disruption and displacement \[[@CR1]\]. Mortality in the early stage after ICH is attributable to increased intracranial pressure (ICP) and tissue shifts \[[@CR2], [@CR3]\]. Transcranial Doppler (TCD) is utilized as an indirect measure of ICP because higher ICP causes characteristic changes of decreased end-diastolic flow velocity (Vd) and increased pulsatility index (PI) in the Doppler waveform \[[@CR4]\]. Several studies have confirmed that the PI of the unaffected hemisphere may be a predictor of death in acute ICH, suggesting that intracranial hypertension is the most likely cause of death in patients with ICH \[[@CR5]--[@CR7]\]. However, compared to patients with supratentorial cerebral infarction, patients with supratentorial cerebral hemorrhage are more prone to disturbance of consciousness; that is, changes in consciousness state after ICH, which are not always easily explained on the basis of increased ICP, mass effect, or herniation \[[@CR8]\]. Relief of elevated ICP by ventricular drainage is commonly performed, and may improve the level of consciousness of patients with ICH with coma. Notwithstanding, coma often persists, implicating other causative pathology \[[@CR9]\].

The secondary pathophysiological processes of ICH include progress in cerebral edema \[[@CR10]\], activation of apoptotic processes \[[@CR11]\], and the toxic effects of hematoma components \[[@CR12], [@CR13]\]; these factors can cause severe, persistent damage. Functional imaging with PET indicated that surrounding the hematoma was a region of reduced cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO~2~), and oxygen extraction fraction (OEF) \[[@CR14]\]. Combined application of Xenon CT and PET in previous studies on CBF and CMRO~2~ has also shown that EEG changes can reflect the coupling of CBF and brain metabolism \[[@CR15]\]. In comparison with primitive EEG, quantitative EEG (QEEG) has an advantage in quantification and interpretation. Delta power measures had the strongest negative correlation with CBF, and alpha power had a relatively strong positive correlation with CBF; increased power in slower frequency bands (delta and theta) and decreased power in faster frequency bands (alpha and beta) are seen with reductions in CMRO~2~ \[[@CR15]--[@CR17]\].

In this study, we sought to investigate whether it is possible to comprehensively evaluate brain function by administering TCD combined with QEEG in patients with severe acute supratentorial (SAS)-ICH, and to assess outcome at the 90-day follow-up; and to explore a new basis for pathophysiological changes in severe ICH.

Methods {#Sec2}
=======

Patients {#Sec3}
--------

In this prospective study, we consecutively enrolled patients with ICH with coma who were admitted to the Department of Neurology, First Hospital of Jilin University, China, between June 2015 and December 2016. The patients were included in our study if they met the following criteria: admission time ≤ 72 h after onset; presence of supratentorial hemorrhage; and Glasgow Coma Scale (GCS) score ≤ 8 points on admission, as assessed by an experienced neurologist. Exclusion criteria were the following: ICH secondary to aneurysm, vascular malformation, tumor, and cerebral infarction; deficient temporal acoustic bone window; scheduled surgical treatments, including ventricular drainage, clot removal, and craniotomies; middle cerebral artery or other intracranial and extracranial major vascular stenosis/occlusion; previous ischemic or hemorrhagic cerebrovascular disease; pathological changes that affect intracranial EEG activity, such as intracranial infection, ischemia anoxic encephalopathy, cerebral trauma, and others; presence of marked environmental turbulence, such as low temperature (core body temperature \< 32 °C), hypoglycemia (\<50 mg/dl), hyponatremia (\<116 mg/dl), and others; and central nervous system depressant use, including sedative, narcotic, antidepressants, antipsychotics, antiepileptic drugs, and others. Fifteen age and sex-matched healthy controls (64.3 ± 13.5 years old, eight men) were recruited. Written informed consent was obtained from each patient's immediate family members before the beginning of the study. The study was approved by the Ethics Committee of the First Hospital of Jilin University, China, and conformed to the tenets of the Declaration of Helsinki.

Clinical data {#Sec4}
-------------

All patients received routine monitoring of vital signs and intensive nursing care in the Neurological Intensive Care Unit. We recorded and analyzed the following variables: demographics (age and sex); stroke risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, previous acute coronary event, smoking, excessive drinking); admission GCS score; time from ICH onset until the time monitoring commenced; whether blood pressure and glucose management were in accordance with current ICH management guidelines \[[@CR18]\]; other admission laboratory tests (serum potassium, calcium, and sodium, white blood cell count, platelet count, activated partial thromboplastin time (APTT), International Normalized Ratio (INR)); neuroimaging variables (for regular hematoma, ICH volume was measured using length × width × depth/2; for irregular hematoma, length × width × depth/3 was adopted \[[@CR19]\]---head CT with hematoma location and volume on admission was evaluated by a neuroradiologist blinded to the clinical and brain function data); and clinical outcome assessed using the 5-point Glasgow Outcome Scale score 90 days after ictus.

TCD-QEEG measurements {#Sec5}
---------------------

Patients were in the supine position during quantitative brain function monitoring. TCD was performed using 2-MHz pulsed-wave Doppler probes fixed to each temporal window with a helmet. The depth of acquiring optimal middle cerebral artery signals was 50--60 mm from both sides. Simultaneous EEG was obtained with standard 16-channel electroencephalography with silver chloride scalp electrodes placed in accordance with the 10--20 system; electrode impedance was maintained below 10 KΩ. The healthy control group remained with their eyes closed and awake during the process. Data were recorded for over 30 min until a stable recording was established; the recorded data were stored for further analysis.

Data analysis {#Sec6}
-------------

Blinded analysis was performed for each patient. All clearly readable TCD waveforms were used in the calculations. The following variables were analyzed: systolic flow velocity (Vs), diastolic flow velocity (Vd), mean velocity (Vm), and PI from the affected and unaffected hemispheres. Vm was calculated using the following equation:$$\documentclass[12pt]{minimal}
                \usepackage{amsmath}
                \usepackage{wasysym}
                \usepackage{amsfonts}
                \usepackage{amssymb}
                \usepackage{amsbsy}
                \usepackage{mathrsfs}
                \usepackage{upgreek}
                \setlength{\oddsidemargin}{-69pt}
                \begin{document}$$ \mathrm{Vm}=\left(\mathrm{Vs}\hbox{--} \mathrm{Vd}\right)/3+\mathrm{Vd}, $$\end{document}$$

and PI was calculated using the following equation:$$\documentclass[12pt]{minimal}
                \usepackage{amsmath}
                \usepackage{wasysym}
                \usepackage{amsfonts}
                \usepackage{amssymb}
                \usepackage{amsbsy}
                \usepackage{mathrsfs}
                \usepackage{upgreek}
                \setlength{\oddsidemargin}{-69pt}
                \begin{document}$$ \mathrm{PI}=\left(\mathrm{Vs}\hbox{--} \mathrm{Vd}\right)/\mathrm{Vm}. $$\end{document}$$

Offline QEEG analysis was performed using MATLAB (MathWorks, Natick, MA, USA). After data filtering (high pass 0.3 Hz, low pass 30 Hz) and all segments of artifact-free EEG were analyzed, spectral power was calculated using Fast Fourier transform (FFT) for each electrode over the 1--30 Hz range. The relative power of the delta (1--3 Hz, RDP), theta (4--7 Hz, RTP), alpha (8--13 Hz, RAP), and beta (14--30 Hz, RBP) frequency bands over all channels were used to calculate the global delta/alpha ratio (DAR) and the (delta + theta)/(alpha + beta) ratio (DTABR). The brain symmetry index (BSI) was calculated according to the following formula:$$\documentclass[12pt]{minimal}
                \usepackage{amsmath}
                \usepackage{wasysym}
                \usepackage{amsfonts}
                \usepackage{amssymb}
                \usepackage{amsbsy}
                \usepackage{mathrsfs}
                \usepackage{upgreek}
                \setlength{\oddsidemargin}{-69pt}
                \begin{document}$$ \mathrm{BSI}\left(\mathrm{t}\right)=\frac{1}{M}\frac{1}{N}\sum \limits_{j=1}^M\left\Vert \sum \limits_{i=1}^N\frac{Rij(t)- Lij(t)}{Rij(t)+ Lij(t)}\right\Vert $$\end{document}$$

with the power of the signal obtained from a particular hemispheric bipolar channel pair *i* (with *i* = 1, 2, ..., *N*) at frequency *j* (or Fourier coefficient, with index *j* = 1, 2, ..., *M*), *N* being the number of channel pairs, *M* being the number of Fourier coefficients, *Rij*(*t*) and *Lij*(*t*) for the right and left hemisphere, respectively \[[@CR20]\].

Statistical analysis {#Sec7}
--------------------

All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) and MedCalc version 11.4.4 (MedCalc Software, Mariakerke, Belgium). In the univariate analysis, data were reported as mean and SD for normally distributed variables and as median and interquartile range (IQR) for nonnormally distributed variables. Categorical variables were presented as percentages. Student's *t* tests and median two-sample tests were used for normally distributed variables. Nonparametric Wilcoxon (Kruskal--Wallis) analysis of variance was used for nonnormally distributed variables. The comparison of categorical variables was performed with the chi-squared test. From these analyses, we could select the variables with some prognostic significance (*p* ≤ 0.001). Then, we performed a backward stepwise logistic regression analysis with death at 90 days as the dependent variable. If a TCD or QEEG measure was statistically associated with survival, we calculated its separated and united sensitivity, specificity, and area under the curve with the aid of receiver operator characteristic (ROC) curves. ROC curves were compared by applying DeLong's test. Calculated two-tailed *p* \< 0.05 was considered statistically significant.

Results {#Sec8}
=======

Basic data {#Sec9}
----------

During a 1.5-year period, 76 consecutive patients were diagnosed with severe, acute, spontaneous supratentorial ICH. The following patients were excluded: admission beyond 72 h from onset of symptoms (*n* = 4), surgical procedure (*n* = 2), macrovascular stenosis (*n* = 7), previous cerebrovascular disease (*n* = 5), deficient temporal window (*n* = 6), signal artifacts (*n* = 3), and loss to follow-up (*n* = 2). Finally, we enrolled 47 patients, of which 26 (55.3%) died during the 90-day follow-up period. The median age was 67.3 ± 12.6 years, and 23 (48.9%) of the patients were male. The first TCD-QEEG was performed a mean of 31.0 (19.0--59.0) h after the onset of symptoms. No statistically significant differences between survivors and nonsurvivors were noted for clinical baseline data, including age, sex, risk factors, blood pressure, serum glucose, serum potassium, calcium, and sodium, white blood cell count, platelet count, APTT, INR, and hematoma location. Only larger hematoma volume (*p* \< 0.0001) and higher Glasgow Coma Scale score (*p* = 0.001) were associated with mortality (Table [1](#Tab1){ref-type="table"}).Table 1Demographic and baseline characteristicsCharacteristicAll patients (*n* = 47)Survivors (*n* = 21)Nonsurvivors (*n* = 26)*p* valueDemographics Age (years), mean (SD)67.3 (12.6)68.8 (12.5)64.1 (12.4)0.21 Male, *n* (%)23 (48.9)9 (42.9)14 (53.8)0.45Risk factors, *n* (%) Hypertension41 (87.2)18 (85.7)23 (88.5)0.77 Diabetes mellitus7 (14.9)3 (14.3)4 (15.4)0.91 Hyperlipidemia13 (27.7)8 (38.1)5 (19.2)0.15 Coronary heart disease13 (27.7)6 (28.6)7 (26.9)0.90 Smoking15 (31.9)5 (23.8)10 (38.5)0.28 Excessive drinking11 (23.4)4 (19.0)7 (26.9)0.53Time from ICH onset to monitor (h), median (IQR)31.0 (19.0--59.0)39.0 (19.0--65.0)26.0 (18.8--46)0.21GCS score, median (IQR)7 (6--8)7 (7--8)6 (4--7)0.001SBP (mmHg), mean (SD)168.4 (30.0)175.3 (25.9)162.7 (32.4)0.16DBP (mmHg), mean (SD)85.2 (21.3)90.5 (18.1)80.9 (23.0)0.13WBC (×10^9^/L), mean (SD)13.0 (3.5)12.5 (4.2)13.3 (2.8)0.44Platelet (×10^9^/L), mean (SD)198.3 (78.9)205.4 (74.5)192.5 (83.2)0.58APTT (s), mean (SD)29.1 (3.4)29.1 (3.7)29.0 (3.1)0.96INR, mean (SD)1.01 (0.09)0.98 (0.09)1.01 (0.10)0.28Glucose (mmol/L), median (IQR)7.6 (6.9--9.4)7.2 (6.8--9.6)7.7 (6.7--9.2)0.86Potassium (mmol/L), mean (SD)3.6 (0.4)3.6 (0.4)3.7 (0.4)0.33Calcium (mmol/L), mean (SD)141.3 (5.5)141.6 (6.2)141.0 (4.9)0.74Sodium (mmol/L), median (IQR)2.2 (2.1--2.3)2.2 (2.1--2.3)2.2 (2.1--2.3)0.40Hematoma side, left, *n* (%)30 (63.9)14 (53.8)16 (76.2)0.11Hematoma location, *n* (%)0.65 Lobe8 (17.0)3 (14.3)5 (19.2) Deep39 (83.0)18 (85.7)21 (80.8)Hematoma volume (cm^3^), median (IQR)45.5 (25.0--75.9)25.0 (19.6--39.6)62.8 (44.1--90.1)\<0.0001Intraventricular hemorrhage, *n* (%)37 (78.7)22 (84.6)15 (71.4)0.27*SD* standard deviation, *ICH* intracerebral hemorrhage, *IQR* interquartile range, *GCS* Glasgow Coma Scale, *SBP* systolic blood pressure, *DBP* diastolic blood pressure, *WBC* white blood cell count, *APTT* activated partial thromboplastin time, *INR* International Normalized Ratio

Evaluation of brain function with TCD-QEEG {#Sec10}
------------------------------------------

Figure [1](#Fig1){ref-type="fig"} shows the CT and TCD-QEEG findings of representative patients.Fig. 1Examples of representative patients. **a** Nonsurvivor patient. QEEG shows the slower delta frequency band significantly increased and the faster alpha frequency band significantly decreased. Moreover, DAR, but not BSI, also increased. TCD shows the PI of bilateral hemispheres significantly increased. **b** Survivor patient. QEEG and TCD show similar changes, but not as significant, to those seen in (**a**). BSI did not increase either. **c** Healthy control patient. QEEG and TCD normal. DAR delta/alpha ratio, DTABR (delta + theta)/(alpha + beta) ratio, BSI brain symmetry index, VS systolic flow velocity, VM mean flow velocity, VD diastolic flow velocity, PI pulsatility index, TCD transcranial Doppler, QEEG quantitative electroencephalography

Regarding TCD relevant indicators, Vd of unaffected hemispheres was lower in nonsurvivors (UVd *p* = 0.018) and the PI of both hemispheres was higher in nonsurvivors than survivors in patients with SAS-ICH (API *p* \< 0.0001, UPI *p* \< 0.0001) (Table [2](#Tab2){ref-type="table"} and Fig. [2b, c](#Fig2){ref-type="fig"}). Vm in the affected hemisphere and Vd and PI in both hemispheres showed significant differences (all *p* \< 0.0001) between patients with ICH and healthy controls (Table [2](#Tab2){ref-type="table"} and Fig. [2a--c](#Fig2){ref-type="fig"}).Table 2TCD and QEEG parametersNonsurvivors (*n* = 26)Survivors (*n* = 21)Healthy controls (*n* = 15)TCD parameters VS (cm/s), mean (SD)  Affected side85.6 (23.9)84.9 (18.4)Overall88.6 (21.4)  Unaffected side91.2 (23.0)89.5 (21.8) VM (cm/s), mean (SD)  Affected side43.8 (13.6)^\*^46.3 (10.5)^+^Overall56.8 (14.8)  Unaffected side48.0 (12.9)51.7 (12.7) VD (cm/s), mean (SD)  Affected side23.6 (9.9)^\*^27.6 (7.0)^+^Overall41.3 (12.0)  Unaffected side26.6 (8.7)^\#\ \*^33.0 (8.9)^+^ PI, mean (SD)  Affected side1.5 (0.2)^\#\ \*^1.2 (0.2)^+^Overall0.9 (0.2)  Unaffected side1.4 (0.2)^\#\ \*^1.1 (0.2)^+^QEEG parametersRDP (%), median (IQR)74.4 (72.5--78.2)^\#\*^70.0 (67.7--73.1)^+^49.7 (40.0--55.9)RTP (%), median (IQR)8.4 (7.2--10.1)^\*^9.5 (8.2--12.0)^+^7.1 (6.4--8.8)RAP (%), median (IQR)9.5 (8.4--10.8)^\#\*^11.9 (10.2--13.2)^+^27.0 (24.8--38.2)RBP (%), median (IQR)6.4 (5.0--7.5)^\*^7.1 (4.2--8.7)^+^12.9 (9.3--15.7)DAR, median (IQR)7.8 (6.8--9.4)^\#\*^6.1 (5.4--6.9)^+^2.0 (1.2--2.6)DTABR, median (IQR)5.1 (4.6--6.0)^\#\*^4.3 (3.7--4.8)^+^1.6 (0.9--1.8)BSI, median (IQR)0.38 (0.33--0.40)^\*^0.36 (0.31--0.40)^+^0.33 (0.29--0.38)*TCD* Transcranial Doppler, QEEG quantitative electroencephalography, *VS* systolic flow velocity, *SD* standard deviation, *VM* mean flow velocity, *VD* diastolic flow velocity, *PI* pulsatility index, *RDP* relative delta power, *IQR* interquartile range, *RTP* relative theta power, *RAP* relative alpha power, *RBP* relative beta power, *DAR* delta/alpha ratio, *DTABR* delta + theta)/(alpha + beta) ratio, *BSI* brain symmetry index^\#^*p* \< 0.05 for nonsurvivors vs survivors^\*^*p* \< 0.05 for nonsurvivors vs healthy controls^+^*p* \< 0.05 for survivors vs healthy controlsFig. 2TCD and QEEG parameters in patients with ICH compared to healthy controls. TCD parameters: **a** affected hemisphere systolic flow velocity (AVS), mean flow velocity (AVM), and diastolic flow velocity (AVD); **b** unaffected hemisphere systolic flow velocity (UVS), mean flow velocity (UVM), and diastolic flow velocity (UVD); and **c** pulsatility index (PI). QEEG parameters: **d** relative band power of delta, theta, alpha, and beta; **e** delta/alpha ratio (DAR) and (delta + theta)/(alpha + beta) ratio (DTABR); and **f** brain symmetry index (BSI). ^\#^*p* \< 0.05 for nonsurvivors vs survivors; \**p* \< 0.05 for nonsurvivors vs healthy controls; ^+^*p* \< 0.05 for survivors vs healthy controls

Regarding QEEG relevant indicators, higher relative delta power (RDP *p* \< 0.0001), lower relative alpha power (RAP *p* \< 0.0001), higher delta/alpha ratio (DAR *p* \< 0.0001), and higher (delta + theta)/(alpha + beta) ratio (DTABR *p* = 0.002) were associated with mortality in patients with SAS-ICH. All indicators except BSI showed significant differences (all *p* \< 0.0001) between patients with ICH and healthy controls (Table [2](#Tab2){ref-type="table"} and Fig. [2d, e](#Fig2){ref-type="fig"}). There were no significant differences in BSI between survivors and nonsurvivors or between patients and controls (all *p* \> 0.05) (Table [2](#Tab2){ref-type="table"} and Fig. [2f](#Fig2){ref-type="fig"}).

Multivariate analysis {#Sec11}
---------------------

All *p* ≤ 0.001 variables in the univariate analysis were entered into a logistic regression model with mortality at 90 days as the dependent variable. The result showed that only DAR (OR 5.306, CI 1.533--18.360, *p* = 0.008) and UPI (adjusted OR 2.373, CI 1.299--4.335, *p* = 0.005) were identified as independent predictors for mortality at 90 days after SAS-ICH. The results of the logistic regression analysis remained unchanged when we excluded the GCS score and hematoma volume to verify model stability.

Comparison of ROC curves {#Sec12}
------------------------

To determine whether the combination of TCD and QEEG variations in the model improved outcome prediction, we compared the ROC curves of five models: the first model was obtained by the GCS score, the second model contained the hematoma volume, the third model was obtained by the independent predictors of TCD with UPI, the fourth model was obtained by the independent predictors of QEEG with DAR, and the final model included both UPI and DAR. All models could predict mortality in patients with ICH at 90 days. The final model attained a high prognostic power, as the area under the ROC curve was 0.949 when UPI and DAR were combined. The contribution of the final model was significant, while each variable alone did not seem to be significant (Fig. [3](#Fig3){ref-type="fig"}).Fig. 3Comparison of ROC curves to predict outcome in this cohort between five models: Glasgow Coma Scale (GCS), AUROC 0.776 (0.630--0.884); hematoma volume, AUROC 0.816 (0.676--0.914); unaffected side pulsatility index (UPI), AUROC 0.822 (0.683--0.918); delta/alpha ratio (DAR), AUROC 0.860 (0.728--0.944); transcranial Doppler (TCD) + quantitative electroencephalography (QEEG), AUROC 0.949 (0.842--0.992). *p* \< 0.05 for TCD (UPI) + QEEG (DAR) comparison with GCS, hematoma volume, UPI (independent predictor of TCD), and DAR (independent predictor of QEEG). AUROC area under the receiver operating curve

Discussion {#Sec13}
==========

To our knowledge, this is the first study that focused on combined application of TCD-QEEG to assess the brain function of patients with SAS-ICH, and its prospective design could provide 90-day prognostic information. The results mainly suggested that TCD parameters of response to ICP and QEEG parameters of response to CBF and brain metabolism were significantly changed; UPI in TCD and DAR in QEEG were two independent predictors for 90-day mortality. Moreover, the area under the ROC curve after the combination of UPI and DAR was 0.949, which was superior to any single variable.

In previous studies, a variety of scales based on clinical data have often been used to assess ICH mortality and prognosis; variables that enter the scale usually include age, NIHSS score, GCS score, blood glucose, location of ICH, hematoma volume, intraventricular hemorrhage, and others \[[@CR21]--[@CR23]\]. After analyzing these clinical variables, we found that only GCS score and hematoma volume were associated with mortality. However, after entering these factors into the multiple regression model, they were not independent predictors. The reason may be that we enrolled patients with coma with GCS score ≤ 8, where GCS score and hematoma volume no longer have significant advantage in predicting prognosis in severe ICH.

TCD can assess intracranial compliance and, to some extent, reflect the level of ICP when it increases. The reason for the increase in ICP may be through a rise in intracranial volume, or secondarily through acute obstructive hydrocephalus \[[@CR24]\]. The progressive increase in ICP and the decrease in cerebral perfusion pressure (CPP) significantly affect the Doppler waveform; typical changes include decreased Vd and increased PI. Mayer et al.'s \[[@CR5]\] study showed that alterations in PI more reliably reflected intracranial lesion volume, and TCD could assess the asymmetry of intracranial hemodynamics. Martí-Fàbregas et al. \[[@CR6]\] suggested that TCD is effective for assessing intracranial hypertension, and elevated UPI can predict 30-day outcome in patients with ICH. Kiphuth et al. \[[@CR7]\] found that early PI monitoring by TCD correlated with ICP, and may be used to predict the outcome after 6 months. Our study on TCD drew a similar conclusion; decreased UVd and increased bilateral PI were significantly correlated with 90-day mortality, and API and UPI were the more significant predictors. Multivariate regression analysis showed that UPI was an independent prognostic factor.

QEEG is capable of quantitatively reflecting changes in intracranial neuronal activity, CBF, and metabolism. Powers used PET-measured CBF and CMRO~2~ in patients with ICH, and found that both perihematomal CBF and CMRO~2~ were significantly reduced compared to the contralateral side \[[@CR25]\]. QEEG changes after ICH have not been reported; many QEEG studies of ischemic stroke have confirmed that QEEG correlates well with CBF and brain metabolism (CMRO~2~) in early subacute ischemic stroke. Finnigan et al. \[[@CR26]\] assessed patients with acute supratentorial infarction, and suggested that DAR and RAP were positively correlated with the 30-day NIHSS score. Cuspineda et al. \[[@CR27]\] reported (sub)acute ischemic stroke RDP to be the most significant and RAP the next best predictor of the 3-month outcome. Finnigan et al. \[[@CR28]\] found that DAR showed maximal accuracy for discriminating between patients with acute ischemic stroke and controls. Our study also showed that the slower frequency band delta power increased and the faster frequency band alpha power decreased with the aggravation of brain injury. RDP, RAP, DAR, and DTABR were all significantly correlated with 90-day mortality; DAR and DTABR were the most significant among them. Multivariate regression analysis showed that DAR was an independent prognostic factor.

Many questions remain regarding the pathophysiological changes in ICH. Severely impaired consciousness is more common with acute supratentorial ICH than with supratentorial infarction ischemic stroke \[[@CR8]\]. Alterations in consciousness following ICH are not always easily explained by increased ICP or herniation. We also found that in some patients with severe supratentorial ICH, clinical indications, state of consciousness, and QEEG indicate that the patient is in a state of exhaustion, but the TCD waveform is normal, and PI is not high in the last few hours of monitoring. Additionally, we found that there was no difference in BSI between severe ICH and healthy controls in QEEG. The BSI is an indicator of bilateral hemisphere damage symmetry, while in ischemic stroke the BSI or pairwise-derived BSI significantly increased, and the degree of increase was significantly related to prognosis \[[@CR29], [@CR30]\]. It may, therefore, be assumed that brain damage in hemorrhagic stroke is diffuse, unlike in ischemic stroke. Neuroimaging has provided objective evidence of damage to the contralateral hemisphere in unilateral ICH. Zazulia et al. \[[@CR31]\] reported swelling of the bilateral hemispheres during the first week following acute supratentorial ICH.

Our study aimed at evaluating the brain function of severe supratentorial ICH using TCD combined with QEEG, and obtained good results, which can be utilized in future research in numerous ways. First, we hope to expand the sample size and obtain the boundary value, which could better guide clinical applications. Second, we could compare brain function of TCD-QEEG with functional imaging, and intensively study the mechanism of ICH. Third, a series of studies have confirmed that there are many similarities between acute ICH and TBI in pathogenesis and clinical manifestations. If TCD and QEEG monitoring of these two groups of patients are performed simultaneously, perhaps we can provide a new basis for the disease pathogenesis. Finally, with the undergoing intensive studies on the pathophysiological mechanisms that follow ICH, new treatment methods are bound to appear. TCD combined with QEEG can dynamically, rapidly, and in a timely manner respond to the changes in brain function before and after treatment.

This study has some limitations. First, this was a single-center study in a university hospital setting, and the sample was relatively small. Thus, prospective validation in different settings and with larger samples is needed. Second, we only monitored the patients in the acute phase, and did not perform dynamic monitoring, which is helpful in comprehensively understanding the changes of brain function with disease progression. Well-designed multicenter TCD combined with QEEG dynamic monitoring studies with a larger sample are urgently needed in the future to provide more information for understanding brain functional changes after ICH.

Conclusions {#Sec14}
===========

This study demonstrated that in patients with SAS-ICH, brain damage caused diffuse changes, evident with multimodality neuromonitoring of TCD combined with QEEG; UPI and DAR were independent predictors of 90-day clinical outcome. Diagnostic power after combined use of TCD-QEEG is statistically superior in performance to any single variable, whether clinical or neurophysiological.

APTT

:   Activated partial thromboplastin time

BSI

:   Brain symmetry index

CBF

:   Cerebral blood flow

DAR

:   Delta/alpha ratio

DTABR

:   (Delta + theta)/(alpha + beta)ratio

GCS

:   Glasgow Coma Scale

ICH

:   Intracerebral hemorrhage

ICP

:   Intracranial pressure

INR

:   International Normalized Ratio

PI

:   Pulsatility index

QEEG

:   Quantitative electroencephalography

RAP

:   Relative alpha power

RBP

:   Relative beta power

RDP

:   Relative delta power

RTP

:   Relative theta power

TCD

:   Transcranial Doppler

Vd

:   Diastolic flow velocity

Vm

:   Mean flow velocity

Vs

:   Systolic flow velocity

The authors thank Qiang Zhang and Ying Wang for providing technical assistance in TCD-QEEG monitoring.

Funding {#FPar1}
=======

There are no funding sources to declare.

Availability of data and materials {#FPar2}
==================================

The datasets collected and/or analyzed during this study are available from the corresponding author on reasonable request.

YC contributed to study conception and design, data collection, analysis and interpretation, and drafting of the manuscript. YqX and JcF contributed to study conception and design, analysis and interpretation of the data, and revision of the final manuscript. WhX contributed to study conception and design, analysis and interpretation of the data, and revision of the manuscript. LjW contributed to data collection and revision of the manuscript. XmY contributed to study conception and design, data collection, and analysis and interpretation. JC and FD contributed to study conception and design and revision of the manuscript. All authors gave final approval of the version to be published.

The study was approved by the Ethics Committee of the First Hospital of Jilin University, and written informed consent was provided by each patient's next of kin/participant.

Consent for publication {#FPar3}
=======================

Written informed consent was obtained from each patient's next of kin/participant for publication of their individual details and accompanying images in this manuscript.

Competing interests {#FPar4}
===================

The authors declare that they have no competing interests.

Publisher's Note {#FPar5}
================

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


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Does that mean he’s played by Michael Dorn?

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Another New Character for this November!


Facade
(185) Provide a unified interface to a set of interfaces in a
subsystem. Facade defines a higher-level interface that makes the subsystem
easier to use.

Flyweight
(195) Use sharing to support large numbers of fine-grained
objects efficiently.

Proxy
(207) Provide a surrogate or placeholder for another object to
control access to it.

Behavioral Patterns

Chain of Responsibility
(223) Avoid coupling the sender of a request to
its receiver by giving more than one object a chance to handle the request.
Chain the receiving objects and pass the request along the chain until an
object handles it.

Command
(233) Encapsulate a request as an object, thereby letting you
parameterize clients with different requests, queue or log requests, and
support undoable operations.

Interpreter
(243) Given a language, define a represention for its
grammar along with an interpreter that uses the representation to interpret
sentences in the language.

Iterator
(257) Provide a way to access the elements of an aggregate
object sequentially without exposing its underlying representation.

Mediator
(273) Define an object that encapsulates how a set of objects
interact. Mediator promotes loose coupling by keeping objects from referring to
each other explicitly, and it lets you vary their interaction independently.

Memento
(283) Without violating encapsulation, capture and externalize
an object's internal state so that the object can be restored to this state
later.

Observer
(293) Define a one-to-many dependency between objects so that
when one object changes state, all its dependents are notified and updated
automatically.

State
(305) Allow an object to alter its behavior when its internal
state changes. The object will appear to change its class.

Strategy
(315) Define a family of algorithms, encapsulate each one, and
make them interchangeable. Strategy lets the algorithm vary independently from
clients that use it.

Template Method
(325) Define the skeleton of an algorithm in an
operation, deferring some steps to subclasses. Template Method lets subclasses
redefine certain steps of an algorithm without changing the algorithm's
structure.

Visitor
(331) Represent an operation to be performed on the elements of
an object structure. Visitor lets you define a new operation without changing
the classes of the elements on which it operates.

Head First Design Patterns

Our focus is on the core patterns that matter from the original GoF patterns,
and making sure that you really, truly, deeply understand how and when to use
them. You will find a brief look at some of the other patterns (the ones
you're far less likely to use) in the appendix.

The GoF patterns discussed in detail:

Strategy (p24)

Observer (p44)

Decorator (p88)

Factory Method (p131)

Abstact Factory (p153)

Singleton (p171)

Command (p201)

Adapter (p241)

Facade (p264)

Template Method (p286)

Iterator (p325)

Composite (p356)

State (p410)

Proxy (p460)

The GoF patterns briefly introduced:

Bridge (p612)

Builder (p614)

Chain of Reponsibility (p616)

Flyweight (p618)

Interpreter (p620)

Mediator (p622)

Memento (p624)

Prototype (p626)

Visitor (p628)

Design Principles

Encapsulate what varies (p9)

Program to interfaces, not implementations (p11)

Favor composition over inheritance (p23)

Strive for loosely coupled designs between objects that interact (p53)

Classes should be open for extension but closed for modification (p86)

Design Patterns Explained

A customer review @ Amazon ... "I picked up this book after reading through the
original GoF Design Patterns. Although they discuss similar topics and this
book refers to the GoF book quite frequently, I wouldn't necessarily associate
the two with each other despite having similiar book titles. There isn't much
code or elaborate examples in this book, but it is easily read and understood
by any level of programmer. In my opinion though you should probably read this
book first before you read the GoF book despite this one actually being the one
that is supposed to explain the other. To me it felt more like a synopsis and
is too brief in many places. More or less it makes a good introduction into
design patterns, but it is not the book that will give you a full understanding
of patterns."

The authors do not introduce all 23 GoF patterns. Those discussed are:

Abstract Factory

Factory Method

Singleton

Adapter

Bridge

Facade

Decorator

Observer

Strategy

Template Method

UML and GRASP Patterns

The critical design tool for software development is a mind well educated
in design principles. It is not the UML or any other technology. — Craig Larman

GRASP (General Responsibility Assignment Software Patterns) are
guidelines for assigning responsibility to classes and objects in OO design.
They are really a mental toolset, a learning aid to help in the design of
object oriented software. The patterns and principles specified by GRASP are ...

Information Expert

Look at a given responsibility, determine the information needed to fulfill
it, and then determine where that information is stored. Information Expert
will lead to placing the responsibility on the class with the most information
required to fulfill it.

Creator

Creation of objects is one of the most common activities in an
object-oriented system. Which class is responsible for creating objects is a
fundamental property of the relationship between objects of particular classes.
In general, a class B should be responsible for creating instances of class A
if one, or preferably more, of the following apply:

Instances of B contains or compositely aggregates instances of A

Instances of B record instances of A

Instances of B closely use instances of A

Instances of B have the initializing information for instances of A and pass it on creation.

Controller

Assign the responsibility of dealing with system events to a non-UI class
that represents the overall system or a use case scenario. A Controller object
is a non-user interface object responsible for receiving or handling a system
event. It should delegate to other objects the work that needs to be done; it
coordinates or controls the activity. It should not do much work itself.

Low Coupling

Refers to the degree of direct knowledge that one class has of another.
This supports: low dependency between classes, low impact in a class due to
changes in other classes, and high reuse potential.

High Cohesion

Keep objects appropriately focused, manageable and understandable. High
cohesion is generally used in support of Low Coupling. High cohesion means that
the responsibilities of a given element are strongly related and highly
focused. Breaking programs into classes and subsystems is an example of
activities that increase the cohesive properties of a system. Alternatively,
low cohesion is a situation in which a given element has too many unrelated
responsibilities. Elements with low cohesion often suffer from being hard to
comprehend, hard to reuse, hard to maintain and adverse to change.

Polymorphism

Promote common interface to a base class, and bury peculiar implementation
details in derived classes. The client of the abstraction hierarchy should
then couple itself only to the base class. Another way this has been descirbed
is: the responsibility of defining the variation of behaviors based on type is
assigned to the types for which this variation happens.

Pure Fabrication

Invent a class that does not represent a concept in the problem domain.
It is conceived to achieve low coupling, high cohesion, and reuse potential
across the classes that represent domain concepts.

Indirection

Assign the responsibility of mediation between two elements to an
intermediate object. An example of this is the introduction of a controller
component for mediation between data (model) and its representation (view) in
the Model-View-Controller pattern.

Protected Variations

Protect elements from the variations on other elements (objects, systems,
subsystems) by wrapping the focus of instability with an interface and using
polymorphism to create various implementations of this interface.


Biochemical aspects of inner ear fluids and possible implications for pharmacological treatment.
Inner ear fluids are in dynamic equilibrium with surrounding fluids, namely blood and cerebrospinal fluid. It is known that substances injected into the blood stream or cerebrospinal fluid are transported into the inner ear fluids. The rate of transport from blood into perilymph is inversely related to the molecular weight or molecular size. There appears to exist a blood-labyrinth barrier. In general, the morphology of capillaries in the spiral ligament and stria vascularis is similar to that of brain capillaries which contribute to formation of the blood-brain barrier. Information on the volume of the inner ear fluids is necessary for estimating the toxicity of the drugs as well as the effective concentration of systemically injected substances. Recently, alteration of the levels of arachidonic acid metabolites, especially the prostaglandins, in perilymph under experimental conditions has been reported. The responses of prostaglandin levels in perilymph to these experimental conditions (aspirin injection, antidiuretic hormone or epinephrine infusion) suggest that prostaglandins may play an important role under physiological conditions. Possible mechanisms of auditory dysfunction due to abnormal prostaglandin metabolism in the auditory system are discussed.