**2.1. Primary data collection**

Primary data collection is generally based on field survey comprising three main parts: (a) household interviews, (b) key informant interviews, and (c) focus group discussions.

The research team, led by the principal investigator, visited ten villages in Thatta, Sujawal, and Badin districts in Sindh and in the Gwadar district of Balochistan. The team was assisted by representatives of the communities for interpretation and to translate the questions and answers for both parties (**Figure 3**).

**Figure 3.** Discussion carried out with women at Sonth Village living at the bank of Basool River where it falls into sea.


2.2.2. Graphene Oxide

Another carbon-based nanomaterial for use in biomedical applications is graphene oxide. Nano-graphene oxide complexes, especially metal nanocomposites (nanogold and nanosilver), have been found to be a good choice of material to treat cancer. Due to their greater drug entrapment capability and photothermal and synergizing effects, it is worth highlighting them for their targeted treatment of cancer based on their chemo-thermal behavior.

Chauhan et al. [29] selected gold NPs (AuNPs) as the composite metal and folic acid (FA) as the graphene oxide surface functionalization moiety for active tumor targeting of the model anticancer drug DOX (see Figure 4). Yang et al. [30] have examined the uptake of graphene oxide which has been functionalized with PEG, noting that it has good solubility and biocompatibility. In addition to this, PEG-ylated graphene oxide, which accumulates in tumors and has low retention in the reticuloendothelial system, has also been reported [30].

**Figure 4.** Tumor-localized DOX delivery with simultaneous photothermal ablation [29]. Reproduced with copyright permission from Elsevier, 2017. Legend: FA, folic acid; GO, graphic oxide; AuNPs, gold NPs.

Moreover, Huang et al. [31] have reported that the magnetic functionalized graphene oxide composite may be used as a nanocarrier for the delivery of anticancer drugs. Magnetic graphene oxide was produced by the authors by chemical co-precipitation of Fe3O4 magnetic NPs on graphene oxide nano-platelets. Furthermore, magnetic graphene oxide was modified by chitosan and mPEG-NHS through covalent bonds to synthesize mGOC-PEG. Irinotecan (CPT-11) or DOX was loaded to mGOC-PEG. Another experiment has been reported by Barahuie et al. [32] in which graphene oxide was synthesized in order to explore its potential use as a nanocarrier for an active anticancer agent, chlorogenic acid (CA).

DOX-loaded PEG-ylated nanographene oxide (NGO) preparation has been reported by Zhang et al. [33] where this combination caused destruction of a tumor without recurrence. Qin et al. [34] have used FA-conjugated NGO-PVP as a carrier for DOX, where folate receptors of cancer cells possessed great affinity to bind with folic acid. The FA-NGO-PVP was delivered within the cytoplasm of folate receptor positive human cervical cancer cells (HeLa). The minimal cellular uptake for the nanocarrier was an indication of the adhering of the FA-NGO-PVP composites to the folate receptors on the surface of the A549 cells. Thus, the nanocarrier was shown to have photo-thermal sensitivity and could be used as an anticancer carrier for chemo-photothermal therapy. Furthermore, camptothecin (CPT) and DOX were involved in the sulfonated NGO sheets, where folic acid was attached to carboxyl groups of the sulfonate NGO sheets to deliver DOX. The cytotoxicity of FA-NGO/CPT/DOX to MCF7 human breast cancer cells has been highlighted elsewhere [35]. Zhao et al. [36] have also prepared pH-responsive chitosan/ graphene oxide nanohybrids to be used for the delivery of DOX anticancer.

Liu et al. [37] have functionalized NGOs with PEG, using these to deliver the SN38 anticancer drug for colon cancer. Masoudipoura et al. [38] have reported a nanographene oxide conjugated with dopamine (DA-nGO) and laden with the anticancer drug methotrexate (MTX) to be supplied to positive human breast adenocarcinoma though adhering to DA receptors. GOs have demonstrated better characteristics when compared to CNTs, owing to their greater drug encapsulation ability. However, their use in biomedical applications is still limited because of their complicated synthesis and lower production yield, which makes them uneconomical.


**6. Discussion**

served at baseline (10 min) and after 1 hour of incubation with the substrates. smCS induced slightly higher aggregation of platelets (5-6%) compared to plastic (2.5%) or glass (less than 2%). However, these differences have to be considered with caution, as the coefficient of var‐

**Figure 4.** Fluorescence microscopy (100X)images of human platelets immunodecorated with CD62P (p-Selectin). Ar‐

Platelet activation was studied by the membrane expression of P-Selectin using the CD62P antibody. The expression of P-Selectin was evident on platelets adherent to plastic and glass

On glass and plastic (see arrows) the analysis of morphology showed several fully spread platelets expressing pseudopodia with the occurrence of focal clumps. This was also evident when platelets were examined by Scanning Electron Microscopy, SEM (Figure 5B and 5C).

SmCS film (Figure 5A) induced very limited morphological changes over the 90 minutes of

contact: platelets remained mostly discoid without the occurrence of pseudopodia.

surfaces and was negligible on platelets settled on smCS films (Figure 4).

rows indicate the presence of pseudopodia.

**5.11. Platelet activation assay**

iation estimated with human plasma in the absence of ADP was around 10%.

168 Advances in Biomaterials Science and Biomedical Applications

For blood-contact applications, haemocompatibility is largely determined by specific inter‐ actions with blood and its components [16]. Many, if not all, blood-contacting biomaterials are able to cause different undesired host responses like thrombosis, inflammatory reactions and infections.

The coagulation system and platelets are the main factors for thrombus formation on bioma‐ terials and represent a major unmet problem in the design of vascular implants and bloodhandling systems [17].

It is known that the endothelium is an active organ that maintains vessels integrity and pre‐ vent thrombosis and intimal hyperplasia [18,19]. Hence, biomaterials able to promote *in situ* endothelialisation of implants would be highly desirable.

Studies involving in vitro endothelialisation of grafts with cultured endothelial cells prior to implantation have shown that a confluent endothelium is able to prevent trombogenic complications and improves long-term patency [20,21]. Thus, taking into account that the endothelialisation of the blood-contacting polymeric materials is an important pre-requi‐ site for the success of the synthetic vascular grafts [22] we firstly investigated the ability of endothelial cells to adhere and proliferate on smCS film. The results obtained, in agreement with those shown in our previous paper [13], showed only little variation among the surfaces tested (glass, plastic and smCS). However, from the cell proliferation and morphology it was very difficult to discriminate difference in cytophilicity among the surfaces tested. Furthermore, the presence of fragmented smCS did not induce any decrement in the total number of endothelial cells compared to latex that, on the contra‐ ry, strongly affected cell survival.

The high hydrophilicity of smCS, indicated by the low contact angle, could ease the interac‐ tion with the bipolar extra-cellular matrix proteins such as fibronectin and vitronectin. Fur‐ thermore, the reduced cationic nature, due to a water shell does not allow anionic proteins such as collagen and fibronectin to dissociate from CS surface in a physiological environ‐ ment. This aspect is in agreement with the conclusion of [23] who reported that a hydrophil‐ ic surface is good for anti-non-specific protein adsorption. It was recently reported that the affinity for water of the cell-material interface seems to be a chief parameter in controlling cell adhesion, migration and differentiation [24].

Stevens and George [25] recognized that cells are sensitive to microscale patterns of chemis‐ try and topography, and Dalby [26] noted that cell behaviour is directly influenced by the surface structures such as grooves, pits, or ridges.

In this paper AFM images of smCS films evidenced a topographically patterned surface. In the light of the above reported literature, this observation can be used to speculate about the enhanced adhesion and proliferation of vascular cells compared to conventional, CS films previously observed in [13].

Surface properties such as wettability, surface topography and charge are known to affect endothelial cells attachment and growth [8]likely by altering the rate of the amount of adsor‐ bed proteins and their conformational changes [27,28]. The effect of surface materials on er‐ ythrocyte aggregation and platelet adhesion/activation becomes a chief parameter in haemocompatibility studies.

Several years ago Malette and co-workers [29] ascribed the pro-coagulation properties of chitosan to the negative charged surface of erythrocytes, while [30]showed that chitosan may induce the adhesion of erythrocytes.

In the present study, the surface of smCS films induced only a limited erythrocytes agglom‐ eration, thus indicating that smCS surface neither captures erythrocytes nor forms a threedimensional network structure with these cells.

The lack of erythrocyte aggregation may be likely due to a polymer chains rearrangement that masks the cationic nature of chitosan surface. Such a rearrangement can be ascribed to the larger amount of water in smCS films as described in [13].

One of the most important findings of this work is the observed difference in platelets mor‐ phology seeded on smCS in comparison with glass or plastic. On the latter surfaces platelets appeared flat with interconnecting pseudopodia coupled to strong P-Selectin membrane ex‐ pression.On the contrary, the platelets on smCS films were discoidal, and neither pseudopo‐ dia formation nor a P-Selectin membrane translocation was observed.

This finding could be attributed to a new conformation of the adsorbed plasma proteins on glass or plastic that could have facilitated platelet aggregation. Indeed, it is well known that the surface topography can induce a spatial reorganization of adsorbed proteins as well as how this phenomenon occurs [31]. In contrast, when the adsorbed proteins maintain their native state, they do not support platelet adhesion and aggregation [32].

The absence of platelet activation on smCS surfaces suggests this outcome.

complications and improves long-term patency [20,21]. Thus, taking into account that the endothelialisation of the blood-contacting polymeric materials is an important pre-requi‐ site for the success of the synthetic vascular grafts [22] we firstly investigated the ability of endothelial cells to adhere and proliferate on smCS film. The results obtained, in agreement with those shown in our previous paper [13], showed only little variation among the surfaces tested (glass, plastic and smCS). However, from the cell proliferation and morphology it was very difficult to discriminate difference in cytophilicity among the surfaces tested. Furthermore, the presence of fragmented smCS did not induce any decrement in the total number of endothelial cells compared to latex that, on the contra‐

The high hydrophilicity of smCS, indicated by the low contact angle, could ease the interac‐ tion with the bipolar extra-cellular matrix proteins such as fibronectin and vitronectin. Fur‐ thermore, the reduced cationic nature, due to a water shell does not allow anionic proteins such as collagen and fibronectin to dissociate from CS surface in a physiological environ‐ ment. This aspect is in agreement with the conclusion of [23] who reported that a hydrophil‐ ic surface is good for anti-non-specific protein adsorption. It was recently reported that the affinity for water of the cell-material interface seems to be a chief parameter in controlling

Stevens and George [25] recognized that cells are sensitive to microscale patterns of chemis‐ try and topography, and Dalby [26] noted that cell behaviour is directly influenced by the

In this paper AFM images of smCS films evidenced a topographically patterned surface. In the light of the above reported literature, this observation can be used to speculate about the enhanced adhesion and proliferation of vascular cells compared to conventional, CS films

Surface properties such as wettability, surface topography and charge are known to affect endothelial cells attachment and growth [8]likely by altering the rate of the amount of adsor‐ bed proteins and their conformational changes [27,28]. The effect of surface materials on er‐ ythrocyte aggregation and platelet adhesion/activation becomes a chief parameter in

Several years ago Malette and co-workers [29] ascribed the pro-coagulation properties of chitosan to the negative charged surface of erythrocytes, while [30]showed that chitosan

In the present study, the surface of smCS films induced only a limited erythrocytes agglom‐ eration, thus indicating that smCS surface neither captures erythrocytes nor forms a three-

The lack of erythrocyte aggregation may be likely due to a polymer chains rearrangement that masks the cationic nature of chitosan surface. Such a rearrangement can be ascribed to

ry, strongly affected cell survival.

170 Advances in Biomaterials Science and Biomedical Applications

cell adhesion, migration and differentiation [24].

surface structures such as grooves, pits, or ridges.

previously observed in [13].

haemocompatibility studies.

may induce the adhesion of erythrocytes.

dimensional network structure with these cells.

the larger amount of water in smCS films as described in [13].

As far as the surface morphology is concerned, it has been reported that platelets adhere in similar manner on smooth and rough surfaces when tested under static conditions [33]. Sim‐ ilarly Ward et al. [34] concluded that it is not the roughness *per se* which affects the platelet adhesion.

One decade ago, Suzuki and Minami [35,36] showed that Chitosan depleted complement proteins from plasma, suggesting that chitosan activates complement. A greater depletion of complement activity was seen for a highly de-acetylated form of chitosan [36]. It is however, important to note that the results obtained about the complement activation were based on binding and depletion assays. This complement depletion can equally be explained by as‐ suming a tight binding to the chitosan surface without activation [37].

The results presented here indicate that although large amounts of serum were deposited on smCS surface no activation of the complement system occurred, suggesting that the comple‐ ment is not directly activated by the smCS surface in the process of blood coagulation.

Haemolysis testing of biomaterials has been advocated for, and used in, standard biological safety testing of materials for more than 30 years. The results of test for haemolysis should be considered with care even if they represent the only recommended test for some medical devices as stated in Part 4 of ISO 10993 guideline.

Different papers have reported that chitosan promotes surface-induced haemolysis likely through an electrostatic interactions [38]. In the present work, in the presence of whole blood smCS triggered less than 5% of haemolysis that, along with the low erythrocyte adhe‐ sion, indicates a wide safety margin in blood contacting applications and suitability for vas‐ cular implants.

In the process of haemostasis, the activation of platelet adhesion and aggregation could rep‐ resent an initial and critical step. Here we showed that the surface of smCS films does not interfere with coagulation mechanism and supportswell endothelial cell adhesion and pro‐ liferation even if [39] reported that the haemostatic mechanism of chitosan may be inde‐ pendent of the classical coagulation cascade.


**10.1 Neglected causes of cardiovascular diseases and their causes**

Neglected CVDs in SSA are endomyocardial fibrosis, congenital heart diseases, and rheumatic heart disease [26]. Rheumatic fever affects children in low resource settings where poverty is rife, overcrowding and poor sanitary conditions and limited access to health care services. Rhematic heart disease can be prevented by preventing streptococcal infections or treating them early when they occur [27].

Congenital heart disease: Genes and environmental factors are associated with congenital heart diseases. Maternal health is critical particularly during the first trimester [28]. New-born heart health is affected by maternal health during pregnancy and the environmental conditions in which the mother lives. Causes of endomyocardial fibrosis are virus infections and toxic insults among others [29, 30]. See **Table 1** below.

It is important to point out that social determinants of health are alluded to in the national development plan 2030 [31]. The realisation and implementation of these policies however, remain a challenge.

**9**

**Figure 2.**

security etc.

*Poverty Is Not Poverty: The Reality on the Ground Including the Rural-Urban Divide…*

2020. This includes population and individual based strategies.

• Legislation for reduction of sodium in processed foods [32]

• Detection, treatment and control of cardiovascular disease risk [25]

• Emphasis -assertive treatment, targeting antihypertensive and statin treatment

• Training of nurses (lest we forget) on correct measurement and aggressive management of NCDs, active detection, prevention, control of cardio-vascular

Both the population based and individual based strategies above, are focussing mainly on treatment rather than prevention. Why wait for the population to fall sick? Simple, cost effective and culturally adapted behaviour and educational

Health of the population should be protected- a central tenet of public health. The health care in SA is hospicentric rather than preventive and promotive. Only 10% of health expenditure is spent on promotive health? The system seems to foster

Step 3: Health gives us access to everything else in the society, education, jobs,

Step 1: Health is an asset -acknowledgement and identification of that).

• Taxation of sugar sweetened beverages [32] and alcohol

diseases to avert expenses on hospitalizations [25].

the idea that people should get ill first before being assisted.

**11.1 Population based strategies to prevent NCDs**

• Tightening of anti-tobacco regulations [25]

**11.2. Individual level strategies (crucial)**

guidelines [25]

**12. Public health lip service?**

interventions rather needed (**Figure 2**) [23].

Step 2: Health needs to be preserved.

 South African plans to decrease NCD related premature mortality**

SA has plans to decrease NCD related premature mortality by 25% by end of

*DOI: http://dx.doi.org/10.5772/intechopen.95901*

**Table 1.** *Neglected causes of cardiovascular diseases and their causes.* *Poverty Is Not Poverty: The Reality on the Ground Including the Rural-Urban Divide… DOI: http://dx.doi.org/10.5772/intechopen.95901*


**5. Conclusions**

In this study, the solid–liquid equilibria of a binary 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH][OAc])–water compound system as well as layer and suspension freeze crystallization as a concentration method were investigated. The main conclusions that can be drawn from this study are as follows:

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2073-4352/10/3/147/s1, Figure S1: Schematic diagram of extracting thermal data from a DSC curve, Table S1: Liquidus and glass transition (or eutectic temperature) temperatures extracted from DSC curves, Table S2: Layer freeze crystallization data of aqueous 3 wt.% [DBNH][OAc] solutions with a freezing time of 40 min, Table S3: Layer freeze crystallization data of aqueous 3 wt.% [DBNH][OAc] solutions with a freezing time of 60 min, Table S4: Layer freeze crystallization data of aqueous 6 wt.% [DBNH][OAc] solutions with a freezing time of 40 min, Table S5: Layer freeze crystallization data of aqueous 6 wt.% [DBNH][OAc] solutions with a freezing time of 60 min, Table S6: Suspension freeze crystallization data of aqueous 3 wt.% [DBNH][OAc] solutions with a freezing time of 40 min, Table S7: Suspension freeze crystallization data of aqueous 3 wt.% [DBNH][OAc] solutions with a freezing time of 60 min, Table S8: Suspension freeze crystallization data of aqueous 6 wt.% [DBNH][OAc] solutions with a freezing time of 40 min, Table S9: Suspension freeze crystallization data of aqueous 6 wt.% [DBNH][OAc] solutions with a freezing time of 60 min.

**Author Contributions:** Conceptualization of freeze crystallization experiments, N.O. and M.L.-K.; conceptualization of DSC analysis, L.Y. and H.L.; methodology, validation, and investigation of freeze crystallization, N.O.; methodology, validation, and investigation of DSC analysis L.Y.; writing—original draft, N.O.; writing—review and editing, N.O., L.Y., and M.L.-K.; visualization, N.O. and L.Y.; supervision, M.L.-K. and H.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** The first author is thankful to Aalto CHEM's funding for financial support.

**Acknowledgments:** The authors are grateful to Han Bing and Peter Schulze for their valuable assistance during experimental work as well as to Sanna Hellsten for providing synthetized ionic liquid.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.


*B) Open biopsy*

**2. Neuro-oncologic treatment modalities**

primitive neuroectodermal tumors (PNETs).

– Maximal safe tumor resection when possible

– Histopathological diagnosis

**2.2. Tumor resection**

the extent of resection.

*A) Stereotactic biopsy*

**2.3. Histopathological diagnosis**

The main objectives of the neurosurgeons are as follows:

– Treatment of associated conditions (e.g., hydrocephalus)

appropriate method mainly depends on tumor location.

Neuro-oncology multidisciplinary team discussion allows for a non-bias, more appropriate decision, evident-based, and tailored according to local situation. The option between observation, surgical intervention, radiotherapy, chemotherapy, or a combination of these depends on many factors: tumor type, location, invasiveness as well as the patient's age and overall medical condition. Generally, if a tumor is accessible and the morbidity risk is acceptable, resection should be considered. Neurosurgeons should also actively follow up patients even if a nonsurgical approach is preferred since their interference might be re‐

Thorough evaluation of the patient should be performed before a precise neurosurgical opinion including the clinical condition, neuroimaging studies, and case-specific pertinent investigations (e.g., serum hormone levels, tumor markers, genetic syndrome features, etc.). Imaging of the entire neuraxis should be performed, especially for tumors with a tendency for CNS dissemination such as medulloblastomas, germ cell tumors, ependymomas, and

Maximum safe resection can be performed for a lesion that significant neurological impair‐ ments can be avoided after its surgical removal. The patient's prognosis often correlates with

When pediatric CNS tumors are not amenable to surgical resection, a biopsy is required except in certain situation. Various biopsy techniques have been described and the choice of the

Stereotactic coordinates are used for precise guidance of a needle inside the tumor. This is the method of choice for deeply located tumors. Stereotactic biopsy may be performed through a frameless via frameless neuro-navigation device or a metallic head frame-based system. The

quired for treating unsuccessful cases or complications of the chosen modality.

**2.1. Neurosurgery**

454 Neurooncology - Newer Developments

Open biopsy can be performed through a small craniotomy that allows for direct access to the tumor. This method is traditionally used for superficial tumors near or within the cerebral cortex or when leptomeningeal lesions are identified. Neuro-navigation can help in precise localization of the tumor in relation to the skull surface.

#### *C) Endoscopic endonasal biopsy*

Anterior skull base, sellar region, and tumors invading sinuses can sometimes be accessed through an endoscopic endonasal approach under general anesthesia.

## *D) Endoscopic intraventricular biopsy*

Tumors located adjacent to or within the ventricular system may be amenable to an endo‐ scopic transventricular approach. This procedure has the advantage of allowing treatment of associated hydrocephalus via endoscopic venticulostomy and obtaining intraventricular cerebrospinal fluid (CSF) sample.

## **2.4. Treatment of hydrocephalus**

Due to the mass effect of the tumor causing partial obstruction of the pathway of CSF, hydrocephalus may develop. The main mechanism of hydrocephalus in the context of CNS tumors is obstruction of the ventricular system by tumors in the posterior fossa and that located around the third ventricle [28].

Unstable patients with clinical evidence of elevated ICP should undergo urgent surgery, inserting external ventricular drain (EVD). The anterior horn of the lateral ventricle is accessed through an inserted catheter through a skull burr hole and CSF flow is ensured. The EVD is connected to an external collecting device and allows the excess CSF to be drained [29]. Endoscopic third ventriculostomy (ETV) is another option in hydrocephalus resulting from posterior fossa or pineal region tumors. An ETV creates a communication between the third ventricle and the interpeduncular cistern under endoscopic guidance within the ventricular system [29, 30]. Many patients need permanent diversion of CSF ventriculoperitoneal shunt (VPS). A proximal catheter is inserted inside the lateral ventricle and is then connected to a distal catheter tunneled subcutaneously till it reaches the peritoneum. A valve is commonly inserted between the proximal and the distal catheter and allows for one-way drainage control. One of the disadvantages of VPSs includes the theoretical risk of intraperitoneal seedling of neoplastic cells.

#### **2.5. Spinal cord neoplasms**

Intramedullary spinal cord tumors are rare in the pediatric population, representing around 4% of all CNS tumors. Complete surgical excision if feasible or debulking is the general approach for spinal cord tumors. This procedure often leads to favorable outcome besides providing sufficient materials for histological diagnosis.

#### **2.6. Management of cystic tumors**

Many pediatric CNS tumors are composed of a cystic component or having both cystic and solid parts. The potential space of the cystic portion creates an isolated microenvironment that may hinder local treatment (radiotherapy or local chemotherapy). Simple aspiration of the fluid that composes the cyst may sometimes be a sufficient treatment. Moreover, surgical resection can be considered for most cystic tumors. Local treatment may be applied includ‐ ing the insertion of a device in which medical therapy will be administered. Specifically, the use of intracystic radioisotope (radioactive iodine-125 or phosphorus 32) and intracavitary chemotherapy may be used in selected cases [31]. The main advantage of this treatment is the low rate of long-term sequelae. Intracystic chemotherapy has been advocated to delay aggressive treatment such as radical resection or irradiation. This method allows for admin‐ istration of effective therapy (commonly bleomycin or interferon) and abolishes the systemic toxicity of the systemic chemotherapy and the morbidity of surgical resection. Ommaya reservoir and instillations of single or multiple doses of active drugs remain the method of choice for intracystic chemotherapy.

#### **2.7. Management of tumor recurrence**

The decision to reoperate on a recurred tumor must be taken in the light of the patient's life expectancy and QoL, tumor histology, time length between initial resection and recurrence, the risks and benefits of a second surgery, and the potential for adjuvant therapy such as radiotherapy and chemotherapy. Each case should be individually evaluated through multidisciplinary discussion taking into consideration the patient's family opinion and preference. It is worth emphasizing that surgical treatment of recurrent tumors should be seriously considered as reoperation has improved survival for many tumors such as choroid plexus tumors, ependymomas, and cerebellar astrocytomas [32–34].


4.3.5. Hourly Electricity Load Savings

Figure 16 shows load profiles of house archetypes and specifications for Comfy Heat and E12 tariffs for the coldest winter workday and holiday. Maximum peak loads occur as 4.05 kW in Comfy Heat tariff and 3.94 kW in E12 tariff for all archetypes in the coldest winter workday. Detached houses have the highest energy demand. Therefore, the total variable load is 27.7 kW and 28.8 kW in comfy Heat and E12 tariffs in the unrefurbished category. Semi-detached and end-terraced houses have similar total loads, approximately 19.0 kW in Comfy Heat tariff and 21.0 kW in E12 tariffs.  When houses become more energy efficient, their energy demand reduces, so lower loads are seen in efficient houses. Total heat pump loads in detached houses could be reduced to 20.4 kW in a refurbished house or 13.7 kW with a Comfy Heat tariff in a new building category. Moreover, fewer peaks occur throughout the day. A similar trend occurs in other house archetypes and total heat pump loads could be reduced to 12.7 kW, 11.3 kW, and 12.7 kW for semi-detached, mid-terraced, and end-terraced new building categories, respectively. The coldest winter holiday results also show similar trends but slightly lower load profile results.

This study tries to break down the load results into different house archetypes and specifications so cumulative electricity system load profiles would be more accurate. Each archetype profile is multiplied by the number of houses using heat pumps for all scenarios. Figure 17 shows Orkney electricity system load for baseline, RE, and CE scenarios for the coldest winter workday and holiday. The results are presented for Comfy Heat and E12 tariffs separately and their equally mixed usage scenario. Existing electric loads coming from room heaters are also presented in the figures with yellow bars. The baseline scenario has a limited number of heat pumps deployed. Therefore, the total daily variable heat

pump load is 14.4 MW and 15.4 MW for Comfy Heat and E12 tariffs with 27.9 MW and 26.3 MW peak loads in the coldest winter workday.

**Figure 16.** Average hourly electricity demand load curve of a representative heat pump profile by different archetypes and electricity tariffs for the coldest winter workday and holiday (T: Total, M: Maximum, A: Average).

**Figure 17.** Average hourly electricity demand load curve of heat pump scenarios for Orkney for the coldest winter workday and holiday (T: Total, M: Maximum, A: Average).

RE scenario has high deployment rates of heat pumps (around 80% of total dwellings) so daily total variable heat pump loads reach 168.1 MW and 181.9 MW in Comfy Heat and E12 tariffs with 59.9 MW and 54.7 MW peak loads respectively. Combining both tariffs reduces the peak load to 46.0 MW. When CE scenario has total daily variable heat pump loads with 186.2 MW in Comfy Heat tariff and 202.2 MW in E12 tariff, the peak loads reach 67.7 MW and 62.9 MW in the tariffs, respectively. Comfy Heat tariff has a smaller number of peaks but E12 tariffs have more spread around the day, so the mixed deployment of tariffs helps to reduce peaks to 51.2 MW. When variable heat pump load is compared with constant heat pump load (light red line), the majority of the variable loads stay below constant load, and heat pumps do not operate in the evening, which is when the highest baseload occurs. Peaks are happening in three periods: during the night, before evening and before midnight with two peaks in each. When the coldest holiday results are analyzed, these peaks are even less in the CE scenario with a mixed tariff setting. Only the peak happening before midnight needs to be handled.

Different tariffs create load peaks in different time periods which could be beneficial to combine electricity tariffs to have a more evenly electricity load spread throughout the day. EEI measures help to reduce the total daily variable heat pump load which is crucial to decrease energy demand. However, peak loads remain the same. Therefore, combining more than one electricity tariff in the market could help to reduce peak loads.