**6. MRSA in companion animals**

#### **6.1. Canine and feline MRSA**

The first MRSA from pet animals was isolated from dogs in Nigeria in 1972 [188]. *S. intermedius* is the strain most isolated from dogs [189]. However, the predominant canine species among staphylococci was *S. sciuri* in Japan [190]. Various coagulase-positive and -negative staphylococci have been reported in pet animals [191]. Among coagulase-negative staphylococci, *S. felis* was dominant in Brazil [116], and a coagulase-positive *S. intermedius* was dominant in canine species in the UK [192, 193]. The prevalence of canine MRSA was 0.7% in Portugal, 2.3–9% in UK, and ≤20% in Canada [194–197]. Conversely, in cats, it was 1.48% in the UK, ≤4% in Portugal [195, 198] and 21.4% from wounds and skin lesions of cats in the USA [199]. *S. aureus* was found in 8% of dogs with inflammatory skin disease in the USA and one isolate was MRSA [200]. In addition, one MRSA was detected among the *S. aureus* strains isolated from 29% of 48 cats suffering with inflammatory skin disease and two MRSA were found among the *S. aureus* strains from 20% of 50 healthy cats [201]. Previous surgery, hospitalization, antimicrobial agent treatment, contact with humans possessing MRSA, and use of implant devices are regarded as risk factors for MRSA infection in companion animals [195, 202]. Rich and Robert [203] reported that MRSA were isolated from 1.4% of the postoperative and wound infection samples of pet animals in the UK. Lilenbaum et al. found 3% MRSA in Brazilian cats [193]. Southwest Pacific clone-associated community-acquired MRSA (USA1100) and methicillin-resistant *S. pseudintermedius* (MRSP)-associated with the European clone (ST71) were first reported in South America in cats [204].

MRSA isolates from Austria, Belgium, Germany, Ireland, and Portugal were resistant to ciprofloxacin and enrofloxacin, perhaps because of the fluoroquinolone approval for use in companion animals in Europe in the middle of 1990 (**Table 2**). MRSA ST398 that was identified in dogs and cats in France carried a chloramphenicol acetyltransferase gene, *cat*, that mediates resistance to nonfluorinated phenicols [117]. On the other hand, MRSA isolated in Portugal and Thailand from dogs and Germany from cats possessed a florfenicol-chloramphenicol exporter gene, *fexA*, that mediates resistance to both fluorinated and nonfluorinated phenicols [205–207]. MRSA ST398 isolated from an Austrian dog suffering from vaginitis harbored the *vatC* gene that inactivates streptogramin A [208]. An ABC transporter gene, *lsaE* (responsible for combined resistance to lincosamides, pleuromutilins, and streptogramin A), and a lincosamide nucleotidyltransferase *lunB* gene (confers resistance only to lincosamides), were present in the MRSA ST45 isolated from dogs in Thailand [205]. In France, an MRSA strain (*agr* III-t008–IV) isolated from a synovial fluid of dog was positive for *pvl* [117]. It carried *sek* and *seq* genes and was suspected to be a USA300 variant that was imported from the USA. *tsst1* positive MRSA (*agr* II-t002-SCC*mec* I-truncated) was recovered from pet animals in France (**Table 3**). Leukotoxin genes, most prevalently *lukF* and/or *lukS* followed by *lukD* and/or *lukE*, are reported to be present in most of the MRSA isolated from companion animals, but those from dogs, cats and horses in Austria and the USA did not possess any leukotoxin genes. MRSA isolates CC5-t002–II, CC5-t062 and CC22-t032–IV, isolated in Portugal from a dog, a horse and human, respectively, harbored IEC genes suggesting adaptation to different hosts [206]. The presence of host-adaptive, virulence, and toxin genes makes the companion animal MRSA isolates prime candidates for zoonotic transfer. The first outbreak of human MRSA associated with cats was reported in a rehabilitation geriatric ward in the UK in 1988 [209] but others have since been reported in Australia, Canada, Germany, New Zealand, South America, and the Netherlands [193, 210–212]. Human-associated MRSA, such as EMRSA-15 and CMRSA-2, show a close relationship with pet-associated MRSA [211–214]. Since MRSA ST398 has been isolated from many farm animals, this MLST type found in dogs or cats may have originated from them or people who had contact with them [215]. MRSA SCC*mec* II strains, which are those most frequently affiliated with nosocomial human infections, have been isolated from cats [216].

#### **6.2. Equine MRSA**

were found in dust samples, nasal swabs, and a blood isolate from workers on the same pig farm [177], suggesting multiple acquisitions of SCC*mec* cassettes by MSSA precursors. Coagulase-negative staphylococci in the farming environment are suspected as sources of SCC*mec* [176], and the progeny of emerging MRSA strains are spreading locally rather than globally [178–180]. While SCC*mec* acquisition seems to be fairly common in MRSA ST398, the transfer of staphylococcal toxin genes, including the Panton-Valentine leukocidin gene (*pvl*) appears to be rarer [20, 43, 44, 57, 165, 181–184]. Only a handful of studies have found *pvl* positive ST398 [20, 165, 185–187]. Additionally, horizontal transfer of the protein A gene has been suggested, due to the finding of the *spa* type t899 in both ST398 strains and ST9

The first MRSA from pet animals was isolated from dogs in Nigeria in 1972 [188]. *S. intermedius* is the strain most isolated from dogs [189]. However, the predominant canine species among staphylococci was *S. sciuri* in Japan [190]. Various coagulase-positive and -negative staphylococci have been reported in pet animals [191]. Among coagulase-negative staphylococci, *S. felis* was dominant in Brazil [116], and a coagulase-positive *S. intermedius* was dominant in canine species in the UK [192, 193]. The prevalence of canine MRSA was 0.7% in Portugal, 2.3–9% in UK, and ≤20% in Canada [194–197]. Conversely, in cats, it was 1.48% in the UK, ≤4% in Portugal [195, 198] and 21.4% from wounds and skin lesions of cats in the USA [199]. *S. aureus* was found in 8% of dogs with inflammatory skin disease in the USA and one isolate was MRSA [200]. In addition, one MRSA was detected among the *S. aureus* strains isolated from 29% of 48 cats suffering with inflammatory skin disease and two MRSA were found among the *S. aureus* strains from 20% of 50 healthy cats [201]. Previous surgery, hospitalization, antimicrobial agent treatment, contact with humans possessing MRSA, and use of implant devices are regarded as risk factors for MRSA infection in companion animals [195, 202]. Rich and Robert [203] reported that MRSA were isolated from 1.4% of the postoperative and wound infection samples of pet animals in the UK. Lilenbaum et al. found 3% MRSA in Brazilian cats [193]. Southwest Pacific clone-associated community-acquired MRSA (USA1100) and methicillin-resistant *S. pseudintermedius* (MRSP)-associated with the European

MRSA isolates from Austria, Belgium, Germany, Ireland, and Portugal were resistant to ciprofloxacin and enrofloxacin, perhaps because of the fluoroquinolone approval for use in companion animals in Europe in the middle of 1990 (**Table 2**). MRSA ST398 that was identified in dogs and cats in France carried a chloramphenicol acetyltransferase gene, *cat*, that mediates resistance to nonfluorinated phenicols [117]. On the other hand, MRSA isolated in Portugal and Thailand from dogs and Germany from cats possessed a florfenicol-chloramphenicol exporter gene, *fexA*, that mediates resistance to both fluorinated and nonfluorinated phenicols [205–207]. MRSA ST398 isolated from an Austrian dog suffering from vaginitis harbored the *vatC* gene that inactivates streptogramin A [208]. An ABC transporter gene, *lsaE* (responsible

strains [29, 30, 80, 177].

58 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

**6. MRSA in companion animals**

clone (ST71) were first reported in South America in cats [204].

**6.1. Canine and feline MRSA**

Since the first report of MRSA from mares with metritis in Japan [217], many isolates have been found in Europe, North America, and Asia (**Table 2**) [142–144, 218–220]). Haenni et al. [221] identified four *mecC*-positive MRSA from horses in France exhibiting *spa* types, t208, t843, t6220, t11015 and ST types ST49, ST130, and ST1245. Among them, MRSA CC130 (ST130, ST1245) and CC49 (ST49) were documented in animals and humans, respectively. Multidrugresistant ST8 MRSA was detected in Belgium, Germany, Switzerland, and the USA. A single locus variant of ST8 classified as ST254 MRSA was isolated from horses in Austria, Germany, Ireland, and the UK [183, 208, 222, 223]. Twelve different MLST types have been reported and most of the MRSA strains were grouped into the CC8 or CC398 classes [224]. The CC8-SCC*mec* IV genotype in horses was likely from a contaminated veterinary hospital and later spread to various clinics [219]. This genotype was reported in veterinary hospitals in Canada and the USA [118, 225]. It was first found in infected horses in Ireland and thereafter reported in the Netherlands, Austria, and Germany [226–228]. Many MRSA isolates from Canada showed ST8-SCC*mec* IV-t064 genotype [93]. They were designated as a Canadian epidemic MRSA-5 (CMRSA-5) and were very close to a human clone, USA500. Although the CC8-SCC*mec* IV genotype has been the most frequently found, CC398-SCC*mec* IV has recently become a major genotype. CC398-SCC*mec* IV was first found from infected horses in the Veterinary University of Vienna in Austria [222]. CC398 isolated from nasal samples of horses in the Netherlands and Belgium exhibited high prevalence rates, 9.3 and 10.9%, respectively [227, 229]. More than 25 *spa*-types have been reported, and three types, such as t011, t064 and t451, were the most

Belgium

Belgium

Belgium

Belgium

Belgium

P†

ST9,

+ ++

 +

 ++

 +

 ++

 +++

 ++

*aacAaphD,*

[121]

*aadD,*

*aphA3-sat,*

*blaI, blaR,*

*blaZ, cfr,*

*dfrS1,*

*ermB,*

*ermC,*

*fexA, fosB,*

*lnuA,*

*tetK, tetM,*

*vgaA*

Belgium Belgium Belgium

Brazil

Central

P

9

+++

Europe

 B

 398

+

 ++

P

398

+ +

+

++

+

 +

 +

+

++

 +

*ant4,*

[257]

*aac(6′)-*

*aph(2″),*

*blaZ,*

*mecA,*

*tetK, tetM*

+

+

[258]

 ++

P

398

+ +

+

 ++

 +

 +

P

398

+

+

++

 +

+

+

 ++

 ++

[256]

[66]

[133]

80, 239,

398

 C

 398

+

+

+

+

+

[133]

 C†

239,

++

 +

 +

 ++

 +

+

 +++

 +

398

 B

 398

+ +

+

++

 +

 B†

398

\*

+\*\*

+

++

 +

++

+

 ++

 + +

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

[87]

[133]

[34]

60 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

#### Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 61

Germany

Germany

P

398

+

 ++

 ++

 ++

 + +

+

 ++

+

*aacAaphD,*

[44]

62 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*aadD,*

*blaZ,*

*dfrG, dfrK,*

*ermA,*

*ermB,*

*ermC,*

*fexA,*

*mecA,*

*qacC, tetK,*

*tetL, tetM,*

*vga vgaA*

Hong Kong

Hong Kong P

Hong Kong P

9

+

 +

+ +

+ +

++++

 +

*aacAaphD,*

[134]

*aadD,*

*aadE,*

*blaZ/I/R,*

*dfrK,*

*ermC,*

*lnuB, lsaE,*

*mecA, tetL,*

*spw*

9

+ ++

 +

+

+

 C

 9

+

 ++

 ++

 ++

 + +

 +

+++++

 ++

*aacAaphD,*

[134]

*aadD,*

*aadE,*

*blaZ/I/R,*

*dfrK,*

*ermC,*

*lnuB, lsaE,*

*mecA, spw,*

*tetL*

*ermB,*

[81]

*ermC*

 B

 398

+

+

**+**

+

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

[102]

Italy

Italy

 P

 1

+

 ++

 +

+ +

+++

+

*aacAaphD,*

[119]

*aadD, blaI,*

*blaR, blaZ,*

*cfr, dfrS1,*

*ermA,*

*ermC,*

*ermR,*

*fexA,*

*mecA,*

*qacC,*

*sdrM,*

*tetK, tetM,*

*vgaA*

Italy &

P

 1+

++

 +

+ +

++

 +

*aacAaphD,*

[265]

*aadD,*

*blaZ, cat,*

*dfrA,*

*ermA,*

*ermC,*

*lnuA,*

*mecA,*

*tetK, tetL,*

*tetM,*

*vgaA,*

*vgbA*

Spain

 P

CC97

+

 ++

 +

+ +

+

 +++

 +

*aacAaphD,*

[110]

*aadD, blaI,*

*blaR, blaZ,*

64 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*cat, ermB,*

*ermC,*

*mecA,*

*qacC,*

*sdrM,*

*tetK, tetM,*

*vgaA*

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References** Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 65

Portugal

Spain

 P

398,

+

 +

+ +

++

 +

 +

*aacAaphD,*

[255]

*aadA,*

*aadD,*

*aphA3,*

*dfrA,*

*dfrG, dfrK,*

*ermC,*

*ermT,*

*msrA, str,*

*tetK, tetM,*

*tetL*

+

 +

> +

[234]

[267]

Spain

Spain

 P

1, 398,

++

 +

1965,

1966,

1967,

1968,

1969

Switzerland

 B

 1, 398 +

 +

+

 +

+

*aphA,blaI,*

[42]

*blaR, blaZ,*

*ermC,*

*mecA,*

*tetM*

 P

398

+

 + +

 ++

+

 +

 ++

+

1379

 P

 NA

++

 +

+ +

++

 ++

*aacAaphD,*

[206]

*aadD,*

*apmA,*

66 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*dfrK,*

*ermC,*

*fexA, qacG,*

*qacJ, tetK,*

*tetM, vgaA*

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

> **Table 1.** Antimicrobial resistance pattern of bovine, poultry, and porcine MRSA isolates.

spectinomycin, STR: streptomycin, TET: tetracycline, TIA: tiamulin, TOB: tobramycin, TRI: trimethoprim, SXT: trimethoprim-sulfamethoxazole.

*tetK*

Austria

 D†

22,

\*

+\*\*

+

+

+

+

*aacA-aphD,*

[208]

*dfrA, ermC,*

*tetK, tetM,*

*vatC*

68 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*aacA-aphD,*

[208]

*ermC, tetK,*

*tetM*

254,

398

Austria Austria

Austria

Belgium Belgium

Belgium Belgium

Brazil

Brazil

Canada Canada &

H

 NA

+

+ +

+

USA

China

 C, D

 59, 398

+

+

D

 NA

 +

+++

 +

 ++

+ + +

*aacA-aphD,*

[273]

*ermB,*

*mecA, linA,*

*tetK*

+

+

[271]

[272]

 C

NA

 +

 C

 30

+

H

398

+

 +

+

+

+

+

[229]

[204]

[193]

H

8, 398,

+

 +

++

 +

+

+

2197

 C

 398

D

398

+ + + +

+

+

++

 + +

 +

+ +

+

+

 ++

[133]

[133]

[270]

 H

1, 254,

+

 +

+

+

398

 H†

1, 254,

++

 +

+

+

+

*aacA-aphD,*

[208]

*dfrA, ermC,*

*tetK, tetM,*

*vatC*

*aph2″-*

[222]

*aac6′,*

*ermC,*

*mecA,*

*tetM*

398

C†

1, 5,

++

 +

+

+

398

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

#### Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 69

Japan

Japan

Korea Korea Malaysia

Malaysia Netherlands

Nigeria

Portugal

 D

22,

+ ++

105,

398

Portugal Portugal

Portugal

 H

5, 398

+

 +

 ++

 +

+

+

*aacAaphD,*

[287]

*blaZ, dfrK,*

*ermC,*

*fusC, tetM*

 D

22

++

 +

 ++

 +

+

+

 +

C

 5, 22

++

 +

 +

 D

 NA

 + + + +

 +

 ++

+

+

+ +

*fexA,*

[206]

*ermA,*

*ermC, tetM*

*ermC,*

[206]

*fusC,*

*mphC,*

*msrA*,

*aac(6′)-*

[286]

*aph(2″),*

*ant(4′)-Ia,*

*aph(3′)-*

*III, ermB,*

*ermC,*

*msrA,*

*tetM*

+

[285]

 D

 NA

 +

C

55

+

 D

59

+

D

 NA

 +

 + +

 + + + + +

+

+

+

+

+

+ + + +

 +

[282]

[283]

[283]

[284]

D

72

+

 D

 NA

 +

 D

5, 30

+

+ +

+

+ +

+ + +

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References**

[279]

[280]

[281]

70 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

#### Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 71

**Table 2.** Antimicrobial resistance pattern of feline, canine and equine MRSA isolates.

USA USA

USA USA USA & UK D

USA

 H

8, 830 +

 NA

C

NA

+

 ++ +++

 + +

+ C†: cats, D†: dogs, H†: horses, \*: not tested or sensitive, \*\*: resistant, AMP: ampicillin, CEF: cefoxitin, CHL: chloramphenicol, CIP: ciprofloxacin, CLI: clindamycin, ENR:

enrofloxacin, ERY: erythromycin, FLO: florfenicol, FUS: fusidate, GEN: gentamicin, KAN: kanamycin, LIN: lincomycin, LIZ: linezolid, QD: quinupristin/dalfopristin, SPE:

spectinomycin, STR: streptomycin, TET: tetracycline, TIA: tiamulin, TOB: tobramycin, TRI: trimethoprim, SXT: trimethoprim-sulfamethoxazole.

**Table 2.** Antimicrobial resistance pattern of feline, canine and equine MRSA isolates.

+

+

[118]

+

+

 +

+

C

NA

 D

 NA

C, D

NA

+

 ++

++

++

 +

 +

 +

+

+ + + +

+ +

[294]

[216]

+

[292]

[293]

[293]

72 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

 **Animal ST**

 **AMP CEF CHL CIP CLI ENR ERY FLO FUS GEN KAN LIN LIZ QD SPE STR TET TIA TOB TRI SXT Genotype**

 **References** Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 73

Italy

Cattle

*lukD, lukE,*

*hl, hlIII, hlb,*

*seh*

*hysA1,*

*aur, splA,*

*ssl1, ssl2, ssl3,*

*bbp, clfA,*

*cap8,*

*lmrP, mprF,*

[119]

74 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

*hsdS2, hsdS3,*

*clfB, cna,*

*capH8,*

*ebh, ebpS,*

*capI8,*

*hsdSx*

*icaA, icaC,*

*capJ8,*

*icaD, eno,*

*capK8*

*fib, fnbA,*

*fnbB, sasG,*

*sdrC, sdrD,*

*vwb*

Pigs

*lukD, lukE,*

*hl, hla, hlIII,*

*seh*

*isaB, isdA,*

*aur, splA,*

*ssl1, ssl2, ssl3,*

*bbp, clfA,*

*cap8,*

*lmrP, mprF,*

*hsdS2, hsdS3,*

*clfB, cna,*

*capH8,*

*ebh, ebpS,*

*capI8,*

*hsdSx*

*icaA, icaC,*

*capJ8,*

*icaD, eno,*

*capK8*

*fib, fnbA,*

*fnbB, sasG,*

*sdrC, sdrD,*

*vwb*

[265]

*tsst1*

[91]

Italy &

Pigs

*lukX*

 *hlb*

*entH, entU,*

*entX, entY*

*sed, seg, sei,*

*chp, sak,*

*sej, sem, sen,*

*scn*

*seo, sep, ser*

–

*seb, sed, seg,*

*chp, sak,*

*tsst1*

*sei, sej, sek,*

*scn*

*sem, sen, seo,*

*seq, ser*

–

Spain

Korea

Pigs Chicken

Cattle

*lukE/D, pvl*

*lukE/D*

*lukE/D*

*ssl4, ssl5, ssl6,*

*ssl7, ssl8, ssl9,*

*hysA1,*

*splB, splE,*

*hysA2*

*sspA,*

*sspB, sspP*

*ssl10, ssl11*

*lukF, lukS,*

*hlb, hlgA*

*lukX, lukY*

*ssl4, ssl5, ssl6,*

*ssl7, ssl8, ssl9,*

*hysA2,*

*splB,*

*isaB, isdA,*

*sspA,*

*sak, scn*

*sspB, sspP*

*ssl10, ssl11*

*lukF, lukS,*

*hlgA*

*lukX, lukY*

 **Animals**

**Leukotoxins**

**Hemolysins**

**Enterotoxins**

 **Immuneinvasion**

**Protease**

**Superantigenlike proteins**

**Biofilm- associated**

**Capsule**

**Miscellaneous genes**

**References**

**factors**

**Table 3.** Virulence profiles from food-producing and pet animals.

Methicillin-Resistant *Staphylococcus aureus* (MRSA) in Food-Producing and Companion Animals and Food Products http://dx.doi.org/10.5772/66645 75 widespread [230]. In addition, only three SCC*mec* types (IV, V, VI) have been discovered from horses [218]. Interestingly, no MRSA was isolated from 300 horses on 14 farms in Slovenia, 497 horses on 50 farms in Canada, 87 horses in Austria, and 200 horses in the Netherlands [231–233]. ST22 and ST1117 isolates from horses in Germany had IEC genes, such as *chp, sak*, and *scn* [183]. On the other hand, ST8, ST254, and ST398 strains did not carry those genes.

#### **6.3. Antibiotic resistance and enterotoxin genes in LA-MRSA CC398**

An analysis of MRSA and MSSA from animals and humans spanning 19 countries and four continents indicated that the CC398 lineage originated in humans as MSSA [167]. After its transmission to livestock, CC398 became resistant to tetracycline, probably because of the heavy tetracycline use in pig production [22]. However, many tetracycline-resistant MRSA strains are found in horses despite the fact that tetracycline is either not used much [229] or sparingly used [93, 229]. Among bovine MRSA isolates tested, most of them were resistant to β-lactam antibiotics [34] as well as tetracycline, erythromycin and gentamicin. CC398 has also been reported to be highly resistant to several other antibiotics, such as ciprofloxacin, tobramycin, clindamycin, and trimethoprim-sulfamethoxazole [234]. Antimicrobial resistance patterns of MRSA and MSSA isolates in Hong Kong were very similar [81]. The only MRSA CC398 isolate that has exhibited resistance against daptomycin and intermediate susceptibility to vancomycin has been described in a case-report from an Italian hospital [235]. Two other isolates, one from a ventilator-associated pneumonia of a farmer and one additional porcine isolate, were also described as resistant to linezolid and possessed the *cfr* gene which is located on transferable plasmids [235]. An outbreak with HA-MRSA ST125 containing *cfr*, reported from a Madrid hospital in 2010 [236], was followed by reports on the emergence of nosocomial coagulase negative staphylococci containing *cfr* [40]. This gene was previously found in staphylococci from animals in Europe [237, 238] but has also been reported in humans in Colombia and the USA [239, 240]. Distribution of the *cfr* gene in MRSA isolates is alarming because, besides linezolid, it confers resistance to oxazolidinones, phenicols, lincosamides, streptogramin A, and pleuromutilins, including the topical antibiotic retapamulin that is used for treatment of human skin infections [239, 241, 242].

About 50% of LA-MRSA CC398 isolates, besides being resistant to antimicrobial agents, also exhibit resistance to copper and zinc mediated by the *czrC* gene [130, 243]. The use of zinc as feed additives may have favored spread of the *czrC* gene in LA-MRSA [130]. So far, this gene has only been found in LA-MRSA [130, 243] but an extended use of copper coating of biomaterials in orthopedic surgery and traumatology, as well as copper surfaces in hospitals, might select for *czrC*-positive HA-MRSA as well. The trimethoprim-resistance gene *dfrK*, located close to *tetL* in LA-MRSA ST398, has also been found on a plasmid [244]. The *tetL* gene was identified in MRSA isolated from diverse livestock animals and meats from different regions of the world [97, 245, 246]. Kadlec and Schwarz demonstrated the presence of plasmid pKKS25-associated resistance genes, *ermT, dfrK*, and *tetL*, in MRSA obtained from a nasal swab of a young sow in Germany [247]. A porcine MRSA ST398 was shown to contain a transposon Tn*6133* carrying *ant(9)-Ia* and *ermA* genes and a plasmid pKKS825 [248, 249] harboring the resistance genes *vgaC* and *vgaE, aadD, tetL*, and *dfrK* [248–250]. In Germany, the *vgaE* gene was detected in MRSA ST398 isolated from cattle, turkeys, and chicken and turkey meats [251]. An apramycin resistance gene, *apmA*, was discovered in a bovine MRSA ST398 [252] and in porcine MRSA ST398 [206, 253]. In Denmark, the quaternary ammonium compoundresistant genes, *qacC* and *qacG* were detected in MRSA CC30 isolates [254]. Wendlandt et al. identified a plasmid pV7037-associated multidrug resistance gene cluster, including the novel resistance genes *lsaE* and *spw*, and other resistance genes, such as *mecA, blaZ/I/R, tetL, dfrK, ermC*, and *aadD*, from frozen or chilled chicken carcasses in Hong Kong. The antimicrobial resistance patterns and associated genes from bovine, porcine, and poultry isolates are summarized in **Table 1** and those from companion animals are shown in **Table 2**.

Most of the animal isolates are negative for the *pvl* gene, but Belgian MRSA ST80–IV isolates from healthy pigs were positive for the *pvl* gene and corresponded to the communityacquired CA-MRSA ST80–IV European clone [121]. One Belgian pig CC80 strain contained an exfoliatin (*etd*), an epidermal cell differentiation inhibitor (*edinB*), and staphylococcal exotoxin-like protein (*setC*) and IEC genes (*isaB, isdA, hysA1, hysA2*) [121]. A comparison of the *pvl*-positive MRSA isolates (ST8-t008–IVa) from American pig and pet animals indicated the presence of common virulence profiles (*lukSF-PV, clfA, clfB, fnbA*, and *sek*) except for the *fnbB* gene of a canine isolate [118]. Spanish ST1379/CC97 porcine isolates carried an exfoliatin (*eta*), a leukotoxin (*lukE/D*), and a gamma-hemolysin (*hlg-2*) but were negative for *etb, etc, tst, pvl*, and enterotoxins [255]. The occurrence and prevalence of enterotoxin genes in MRSA isolates from food-producing or companion animals is summarized in **Table 3**. The presence of multidrug-resistant MRSA in companion and food animals, combined with the enterotoxin genes, will require constant monitoring and evaluation of mitigation strategies.


*2.11. Wound Healing Assays*

The mice whose wounds were infected with *S. aureus* were randomly divided into five groups (*n* = 5–7 mice) as follows: blank group, MoS2 group, MoS2-Van-FITC@CS group, NIR MoS2 group, and NIR MoS2-Van-FITC@CS group. The wound site of the blank group was treated with 100 μL of PBS, that of the MoS2 group was treated with 100 μL of MoS2 each day, that of the MoS2-Van-FITC@CS group was treated with 100 μL of MoS2-Van-FITC@CS hydrogel each day, that of the NIR MoS2 group was treated with MoS2, followed by irradiation at 1.5 W/cm2 for 5 min, and that of the NIR MoS2-Van-FITC@CS group was treated with MoS2-Van-FITC@CS, followed by irradiation at 1.5 W/cm2 for 5 min. The mice were photographed daily for eight consecutive days. The mice were euthanized, and their epidermises were harvested for hematoxylin–eosin staining [43].

#### *2.12. Safety Evaluation of MoS2-Van-FITC@CS*

To examine the toxic effects of NIR and MoS2-Van-FITC@CS on the heart, liver, spleen, lungs, and kidneys of mice, the wounded mice were divided into four groups as follows: control group, NIR irradiation group, MoS2-Van-FITC@CS group, and MoS2-Van-FITC@CS + NIR group. The irradiation power density was 1.5 W/cm2, the wavelength was 808 nm, and the irradiation time was 6 min. The mice were treated until their wounds healed, and they were euthanized 30 days after the end of treatment. Their organs were collected, and the cross-sections were stained with hematoxylin–eosin [44].

## **3. Results and Discussion**


*Review* **Role of Surgical Intervention in Unresectable Non-Small Cell Lung Cancer**

**Shigeki Suzuki 1 and Taichiro Goto 2,\***

Received: 29 October 2020; Accepted: 27 November 2020; Published: 29 November 2020

**Abstract:** With the development of systemic treatments with high response rates, including tyrosine kinase inhibitors and immune checkpoint inhibitors, some patients with unresectable lung cancer now have a chance to undergo radical resection after primary treatment. Although there is no general consensus regarding the definition of "unresectable" in lung cancer, the term "resectable" refers to technically resectable and indicates that resection can provide a favorable prognosis to some extent. Unresectable lung cancer is typically represented by stage III and IV disease. Stage III lung cancer is a heterogeneous disease, and in some patients with technically resectable non-small cell lung cancer (NSCLC), multimodality treatments, including induction chemoradiotherapy followed by surgery, are the treatments of choice. The representative surgical intervention for unresectable stage III/IV NSCLC is salvage surgery, which refers to surgical treatment for local residual/recurrent lesions after definitive non-surgical treatment. Surgical intervention is also used for an oligometastatic stage IV NSCLC. In this review, we highlight the role of surgical intervention in patients with unresectable NSCLC, for whom an initial complete resection is technically difficult. We further describe the history of and new findings on salvage surgery for unresectable NSCLC and surgery for oligometastatic NSCLC.

**Keywords:** non-small cell lung cancer; immunotherapy; unresectable; salvage surgery; oligometastasis; targeted therapy


*2.9. In Vitro Digestion*

The EXT, CUB, CUBTAM and yoghurt samples fortified with CUBTAM were subjected to in vitro digestion to identify the bioavailability of bioactive contents using method of Zhang et al. [26] without further modification. The sample (2 mL) was collected before digestion and after oral (5 min), gastric (120 min) and intestinal phases (180 min). The samples were snap frozen using liquid nitrogen to stop enzyme activity and centrifuged at 10,000 RPM at 4 ◦C for 10 min. The supernatants were collected and stored at −20 ◦C before being injected into the LC-MS for phenolic and anthocyanins identification as well as total phenolic content (TPC) and antioxidant activity analysis [13].


*2.3. Seasonal Characteristics*

Firstly, the data of a typical day in spring and summer was selected, respectively. Then, the time-lag curve of temperature and temperature-induced strain was drawn, see Figure 3. It is obvious that the temperature and response strain curve possess typical seasonal characteristics. By comparing Figure 3a,b, it is observed that the hysteresis loop in spring, as shown in Figure 3a, is relatively more compact than that in summer, as shown in Figure 3b. It reflects that in spring the change in temperature is comparatively slower. Hence, the degree of strain response lagging temperature is also less than that in summer. It also gives us a new way to measure the extent of time-lag e ffect through the hysteresis loop area.

**Figure 3.** Plots of strain vs. temperature.

Furthermore, to illustrate the time-lag e ffect as a common phenomenon of concrete box-girder bridges, this paper investigated three months of data. Additionally, the hysteresis loop area of temperature and strain data of every single day are plotted in Figure 4. From Figure 4, a time-lag phenomenon of di fferent extent in almost every day indeed exists. Moreover, the hysteresis loop area in summer (July) is larger than that in winter (November).

In summary, this part gives us a clear understanding of the time-lag phenomenon of temperature effects, a very common phenomenon in concrete box-girder bridges. Moreover, this phenomenon in the form curve annular feature can be directly reflected by the temperature vs. strain graph. Based on the analysis of data in di fferent seasons, a seasonal characteristic was found.

**Figure 4.** Hysteresis loop area in three months of 2017.


All three case studies show how governance systems were caught in a lock-in when it came to zoning wind parks. Essential criteria for area selection were agreed at higher governance levels. Once the zones had been identified, they would quite simply be implemented. In other words, land was earmarked for wind turbines in order to ensure that energy goals would be met. Indeed in all three case studies, the expectation was that by selecting the 'right' locations, implementation would automatically make good progress.

However, once implementation had started, it became obvious that searching for 'alternative' locations would sooner or later be necessary to achieve the targets. The idea that 'the best way to promote the development of wind power is zoning' was not reciprocated at the local level. Despite tighter regulations, many local communities (still) do not agree with having wind farms in their immediate vicinity.

Unfortunately, the findings show that if regional authorities have to come up with alternative locations, these locations will inevitably lie in areas where, according to previous official communications, wind energy deployment has been forbidden. Consequently, as a planning choice, zoning wind energy can become a deterrent rather than an incentive, having established expectations about places where wind turbines are allowed and those where they are not.

The main barriers encountered during implementation were related to a lack of congruency between the actions taken by higher-tier and lower-tier authorities. In South Holland and Lower Austria, local willingness to implement wind energy projects turned out to be weaker than expected. In East Flanders, on the other hand, implementation was blocked by a last-minute manoeuvre of the Flemish Region, which disagreed with provincial zoning decisions. Thus, when the motives of higher and lower tiers of government drift apart, implementation inevitably stalls.

The results also clearly illustrate that zoning alone does not guarantee a sufficiently high level of acceptance of wind energy deployment by the local population. It can even lead to the opposite result. In East Flanders, the publication of a map of 'potential implementations areas' gave rise to immediate opposition at first. Residents feared that wind turbines would be everywhere within the highlighted areas. But public attitude changed when the province invited residents to take part in the planning process and state their preferences.

The reconstruction of the three contextual planning arenas shows that exchanges between higher-tier planning parties and local-level implementation actors were rather marginal. In the Lower Austrian case, we might even talk of deliberate nonparticipation of local actors, since the planning arena was explicitly designed to keep out 'the aggrieved parties'. The expectation was that implementation would be solved by top-down expert decisions. Decision-making clearly lacked the reflexive character for which Healey (1997; 2006) had pleaded in her vision of collaborative practices. In the case of Lower Austria, for instance, the state government criticised large-scale landscape blight through wind turbines but never reconsidered its spatial strategy, which steered wind energy into green areas, nor did it reconsider its energy policy targets.

Hence, planning activities in all three case studies concentrated on the spatial orchestration of sites — the 'territorial indication' (spatial strategy) — rather than the 'strategy to guide future action' (implementation strategy). The practices that guided implementation, independently from the degree to which formal governance levels tried to intervene in local initiatives in favour of wind energy, were designed to comply with goals set at higher governance levels rather than open them to public debate.

## 4.3 Implications

This institutional analysis assessed the effectiveness of wind energy zoning decisions and related governance practices in three urbanised regions of Western and Central Europe. The insights gained thanks to the three case studies allow us to make some general observations, both about effectiveness and practices.

In addition, the purpose of this last section is to review some key issues and discuss their implications for further research on the role of spatial planning in the development of renewable energy production, in particular as regards wind power.

## 4.3.1 Suggestions for action when zoning wind power

The implicit hypothesis of this piece of research was that correlated evidence from the case studies was most likely to be also valid for other regions, i.e. in a comparable institutional setting featuring: the promoting influence of the European Union climate and energy policy, favourable wind conditions, and a high degree of urbanisation. This hypothesis is particularly relevant when it comes to recommendations, raising the following question: to what extent are the 'positively influencing' spatial and governance choices found in the three case study areas transferable?

In order to debate this last question, a feedback workshop was conducted with employees of the Office of the State Government of Upper Austria, in Austria. As in our three case studies, urban sprawl severely constrains wind energy in Upper Austria. There are potential sites on forested hilltops, but these are often locally valued for recreation purposes. At the same time, the state enjoys good climate conditions as regards wind energy generation, which has resulted in growing interest on the part of developers. So far, state policies have been restrictive: neither has the state specified any 2020 goals, nor has it earmarked any land for wind energy.

The text box on the following page documents the outcome of the workshop.

#### Text box 2. Reflection on workshop results

#### Testing the transferability of planning choices

The feedback workshop to test the transferability of planning choices was organised by the author and took place in the city of Linz in February 2017. The participants were public officials and experts in the fields of energy and environmental planning. They were asked to rate the transferability (rather high, probable, or rather low) of a limited set of planning decisions that had been identified during our case studies as institutional drivers.

According to the participants, the majority of the presented procedural parameters to govern wind power initiatives were indeed 'transferable' —particularly those measures that were expected to enhance acceptance by the local population. The table below presents the selected spatial and governance choices and their related spatial-organisational units. These 'suggestions for action' are also *my* recommendations for the various 'planning core actors', in particular those who represent public interests.

#### Suggestions for action when zoning wind power derived from the case studies

The suggestions presented in the text box emphasise the importance of microlevel implementation rules for wind energy zones, projects, and the direct surroundings of a wind park. These include: involvement of the local population in regional planning decisions, requirements for the improvement of areas surrounding wind parks, and stipulations to secure local financial benefits. Regarding higher-tier policies and practices, 'soft' measures that recognise the rhetorical, communicative character of policy and planning were also deemed to be transferable and important, for instance: the positive labelling of zones and associated political commitment to wind power, a more integrative landscape conception promoting the deployment of wind farms through qualitative criteria (e.g. the East Flanders principle of concentration and contrast) and the coupling of planning decisions to a long-term rather than medium-term (2020) renewable energy strategy (e.g. the Lower Austrian energy roadmap). Furthermore, political agreements or coalitions between national and state authorities concerning wind energy targets, as well as agreements or 'memoranda of understanding' between planning and implementation actors on location policy (e.g. wind energy conventions) were deemed to be highly transferable.

However, the results also show that a reversal of previous spatial decisions, or a paradigm shift, is hardly imaginable in this Austrian state. Upper Austria has neither defined wind energy targets nor zoned areas, but it has institutionalised the practice of siting wind turbines far away from residential land-use through strict distance regulations. As a result, locations other than forested tracts (or other agricultural land) were hard to imagine by the workshop participants, as these would usually be in close vicinity to residential areas. Suggested alternative land-use combinations (as practiced in South Holland and East Flanders), in particular the combination with industrial areas, were therefore rated 'low' because, as one expert put it, '*the settlement structure in Upper Austria is very fragmented, highways are nearby residential areas and there are hardly any large, contiguous industrial areas.*'

These insights underline the long-term, prevailing influence of planning decisions regarding spatial restrictions for wind power, which is also one of the key conclusions of the comparative case study analysis. Just as in South Holland, East Flanders and Lower Austria, Upper Austria chose its path in allocating wind energy projects long ago, and this path was determined by land-use choices that, at that time, were considered appropriate. In the meantime, regions have failed to reassess or reconsider the consequences of these choices in the light of technological and economic innovation, and in the light of changing societal attitudes. It will therefore not be easy to modify regional planning policies, even in cases where these plans are facing an implementation deadlock.

Concluding this section, the following figure schematically presents three intermediate levels of governance to which, in my opinion, spatial planning should pay more attention in the future. The suggestions provide for linkages between macro/meso level energy schemes and planning approaches and micro level implementation settings (zones and project-level initiatives).

Figure 32. Synthesis: three important interlinkages between planning and implementation when zoning wind power

Figure by the author

## 4.3.2 Some implications for further research

In all three examined regions, policy-makers were sooner or later confronted with the limited effectiveness of overall, well-considered spatial planning approaches to wind power. What, at the regional level, had been perceived as an innovative plan to combine energy goals with landscape/environmental protection (which are widely supported goals in the planning sector) did not automatically succeed in creating the desired drivers that would motivate local communities to implement projects.

Conversely, planning decisions that largely met with local support were not necessarily compatible with the energy agendas of higher tiers of government. Accordingly, wind power deployment became a task that extended across various spatial-organisational levels and, at each level, gave rise to different perspectives on (desired or undesired) impacts. In this sense, implementation of the three

investigated spatial planning policies was not held back by 'ineffective' planning decisions. Rather, the overall issue was that decisions taken at the planning level insufficiently addressed the concerns of various actors affected by implementation. One of the interviewed experts puts this experience in a nutshell:

*It was very naïve to think we could make a policy that would determine where wind power would be located and where it would not — and that this would work. Even if we do manage to select the right locations, without working on the involvement of residents with wind turbines, we cannot succeed. (Expert 13, administration, 2016)*

This candid interview statement refers to the much-cited resistance from the local population. In a broader sense, however, it can also be interpreted as showing that the examined spatial and governance strategies for wind energy deployment have reached the limits of classical-modernist practices; in particular, this concerns the institutionalised processes that frame decision-making about wind energy locations. There are at least two types of limits that are interesting for further research and these will be discussed in the following paragraphs: (1) reliance on a confined circle of experts and the assumption that zoning leads to a successful implementation and, (2) the limited capacity to reflect on, and adjust established practices.

The first limitation of current practice has to do with the decision-making mechanisms that were used to define wind power zones. The case study results indicate that planning decisions were largely made on the basis of consultation between national or regional authorities and selected experts, who represented the concerns of higher governance levels. Altogether, there was little exchange with the much broader, regionally-varying spectrum of actors who were actively involved in the implementation of projects, for instance: local politicians, private landowners, wind power developers with diverging business models, industry associations, agricultural associations, local residents' initiatives, recreation seekers, or nature protection NGOs. Generally speaking, the concerns of such actors go beyond territorial (resource-aware) considerations of efficient siting they are largely motivated by contextual, economic, and social circumstances.

The second limitation of current practice, which has implications for further research, concerns another recurring theme of the analysis, namely long-term, established land-use restrictions in regional planning affecting wind power deployment. These restrictions are based on fundamental decisions that over the years have never been reconsidered. During the same period, however, considerable economic, technological, and social changes have taken place in and around the wind energy sector. This 'reform resistance' of planning decisions can have unintended side-effects, since it brings with it the risk that technological and social innovations will insufficiently be taken into account. Thus, new approaches

that, over time, might be better aligned with the changing context or changing objectives of renewable energy deployment may well be overlooked.

In conclusion, the above considerations may suggest that the assessment of spatial policies concerning renewable energy should not be limited to identifying those criteria that make wind power zones work as a 'consensus-building device'. Assuming that there are very different patterns at the local level as regards the targets being pursued through wind power deployment, the evaluation of 'effectiveness' could be approached from a different, perhaps more constructive, angle than the 'achieving' or 'not-achieving' of goals.

That is to say, it could be approached from the following perspective: the definition of zoned areas may provide a fertile ground for a directed exchange of views, i.e. the societal exploration of renewable energy issues, which would eventually motivate local communities to wholeheartedly implement projects. In this sense, the outlining of wind power zones is not just a technical act that determines the territorial spread of wind turbines. Rather, it configures socialorganisational entities in which regionally-varying sets of planning and/or implementation actors interact and, in the best case, join forces.

A crucial advantage of the spatial-geographic approach to zoning — in comparison with more neutral approaches such as distance regulations or land-use criteria is that by dealing with the question of 'acceptable locations' it provides spatial planning with opportunities to facilitate local cooperation around wind power. The results of this analysis thereby suggest the formation of zone-based implementation alliances that would mediate between project-level interests and wider, area-based social concerns. In the light of post-2020 renewable energy growth, innovation in planning practices along this path will be necessary. In this way, hopefully, a more fruitful exchange can take place between planning and implementation, allowing 'collective' concerns at higher governance levels to reframe local action as well as enabling local concerns to reshape higher-tier practices.

## Bibliography

Bibliography

Austrian Conference on Spatial Planning, 2011a. *Austrian Spatial Development Concept OREK 2011*. [pdf] Vienna: Austrian Conference on Spatial Planning. Available at:

<http://www.oerok.gv.at/fileadmin/Bilder/2.Reiter-

Raum\_u.\_Region/1.OEREK/OEREK\_2011/Dokumente\_OEREK\_2011/OEREK\_2011\_EN\_Downloadversio n.pdf> [Accessed 3 November 2017].

Austrian Conference on Spatial Planning, 2011b. *H 3.1: Regionales Rahmenkonzept für Windkraftanlagen.* [pdf] Vienna: Austrian Conference on Spatial Planning. Available at:

<http://www.oerok.gv.at/fileadmin/Bilder/2.Reiter-

Raum\_u.\_Region/1.OEREK/OEREK\_2011/good\_practice/Good\_Practice\_Windkraftanlagen\_Bgld.pdf> [Accessed 25 September 2017].

*Austrian Green Energy Act 2012* (GEA 2012), § 4. Vienna: Federal Chancellery of Austria.

Austrian Wind Energy Association, 2016. *Windkraft in Niederösterreich, Die Energie des 21. Jahrhunderts, Juni 2016.* St. Pölten: 2016. Available at:

<https://www.igwindkraft.at/mmedia/download/2016.06.26/1466925772026958.pdf> [Accessed 3 November 2017].

Callens, M., 2014. *Oost-Vlaanderen Energielandschap. Een gereedschapskist voor windlandschappen*. [pdf] Ghent: Oost-Vlaanderen Energielandschap. Available at: <https://www.energielandschap.be/sites/default/files/u11/TOOLKIT.pdf > [Accessed 9 November

2017].

Callens, M., 2015. *Oost-Vlaanderen Energielandschap, Strategisch project, 1 oktober 2011 – 24 december 2014, Eindrapportage.* [pdf] Ghent: Oost-Vlaanderen Energielandschap. Available at: <https://rsv.ruimtevlaanderen.be/Portals/121/documents/projecten/59\_Energielandschappen\_Oost\_V laanderen/2015.02.15\_Eindrapport\_Oost-VlaanderenEnergielandschap.pdf> [Accessed 6 July 2016].

CBS Statistics Netherlands, 2017. [online] Available at:

<http://statline.cbs.nl/StatWeb/publication/?PA=70802NED> [Accessed 12 October 2017].

CONCERE-ENOVER Belgium Federal-Regional Energy Consultation Group, 2010. *Belgium national renewable action plan, pursuant to Directive 2009/28/EC.*

*Convenant Realisatie Windenergie in de Rotterdamse Haven 2009.* (Issued on 15 February). Rotterdam. *Convenant Realisatie Windenergie Stadsregio Rotterdam 2012.* (Issued on 21 June). Schiedam.

Copernicus Land Monitoring Service, 2019. [online] Available at: <https://land.copernicus.eu/> [Accessed 24 July 2019].

Cowell, R., 2010. Wind power, landscape and strategic, spatial planning – the construction of 'acceptable locations' in Wales. *Land Use Policy*, 27 (2010), pp. 222-232.

Dumke, H., Kronberger-Nabielek, P. and Weninger, K., 2016. *Interkommunale Flächenpotenziale Erneuerbare Energie*. [pdf] Vienna / Graz: Technical University of Vienna and Technical University of Graz. Available at:

<https://nachhaltigwirtschaften.at/resources/sdz\_pdf/berichte/ERP\_hoch3\_leitfaden-ap3.pdf> [Accessed 14-09-2017].

Dumke, H., Eder, M., Fischbäck, J., Hirschler, P., Kronberger-Nabielek, P., Maier, S., Malderle, M., Narodoslawsky M., Neber, E.,; Rainer, E., Scheuvens, R., Schnitzer, H., Weinhandl, M., Weninger, K., Zancanella, J. and Zech, S., 2017. *ERP\_hoch3, Abschlussbericht, Energieraumplanung für smarte Stadtquartiere und Regionen*. [pdf] Vienna / Graz: Technical University of Vienna and Technical University of Graz. Available at:

<https://nachhaltigwirtschaften.at/de/sdz/projekte/energieraumplanung-fuer-smart-city-quartiereund-smart-city-regionen-erp-scq-scr.php> [Accessed 01-07-2017].

Perception? The Problems Of Planning – A Developer's Perspective. Wind Farms: More Respectful and Open Debate Needed, Not less. Planning: Problem 'Carrier' or Problem 'Source'? 'Innovative' Wind Power Planning. *Planning Theory and Practice*, 10(4), pp. 521-547.

Environmental Data Compendium, 2014. *Windenergie*. [online] Available at: <http://www.clo.nl/search/site/windenergie> [Accessed 3 November 2014].

<https://ec.europa.eu/energy/sites/ener/files/documents/2012\_energy\_roadmap\_2050\_en\_0.pdf, p. 10> [Accessed 30 November 2017].

*European Commission Directive 2009/28/EC of 23 April 2009 on the promotion of the use of energy from renewable sources.* [pdf] Available at: < http://eur-lex.europa.eu/legalcontent/EN/TXT/PDF/?uri=CELEX:32009L0028&from=EN> [Accessed 3 November 2017]. Strasbourg, 23 April 2009.

Eurostat, 2011. *Degree of urbanisation classification - 2011 revision*. [online] Available at: <http://ec.europa.eu/eurostat/statistics-explained/index.php/Degree\_of\_urbanisation\_classification\_- \_2011\_revision> [Accessed 20 January 2018].

Eurostat, 2018. *Glossary: Tonnes of oil equivalent (toe).* [online] Available at: <http://ec.europa.eu/eurostat/statistics-

explained/index.php/Glossary:Tonnes\_of\_oil\_equivalent\_(toe)> [Accessed 6 January 2018].

<https://www.pbl.nl/sites/default/files/cms/publicaties/pbl-2019-wind-op-land-lessen-en-ervaringen-3379.pdf> [Accessed 24 July 2019].

EWEA European Wind Energy Association. 2017. *Wind Energy Basics*. [online] Available at: <http://www.ewea.org/wind-energy-basics/faq/> [Accessed 3 November 2017].

Feddes, Y., 2010. *Een choreografie voor 1000 molens*. *Windmolens hebben landschappelijk verhaal nodig – deel 2*. The Hague: College van Rijksadviseurs.

Federal Government of the Netherlands, 2009. *Nationaal actieplan voor energie uit hernieuwbare bronnen*. [pdf] The Hague: Federal Government of the Netherlands. Available at: <https://ec.europa.eu/energy/en/topics/renewable-energy/national-action-plans> [Accessed 10 October 2017].

Federal Government of the Netherlands and IPO Interprovinciaal Overleg, 2009. *Klimaat-Energieakkoord tussen Rijk en provincies.* The Hague: Federal Government of the Netherlands and IPO Interprovinciaal Overleg.

Flemish Government, 2000. *Omzendbrief EME/2000.01*. *Afwegingskader en randvoorwaarden voor de inplanting van windturbines.* Brussels: Flemish Government.

Flemish Government, 2006. *Omzendbrief EME/2006/01 - RO/2006/02*. *Afwegingskader en randvoorwaarden voor de inplanting van windturbines.* Brussels: Flemish Government.

Flemish Government, 2014a. *Nota aan de leden van de Vlaamse Regering van 31 januari 2014 betreffende de vastlegging van de jaarlijkse bruto binnenlandse groene stroomproductie en indicatieve subdoelstellingen per hernieuwbare energiebron*. (VR 2014 3101 DOC.0134/1 BIS).

Gasch, R. and Twele, J., eds., 2011; *Windkraftanlagen. Grundlagen, Entwurf, Planung und Betrieb*. 7th ed., Wiesbaden: Vieweg +Teubner | Springer Fachmedien.

Geels, F. and Kemp, R., 2000. Transities vanuit sociotechnisch perspectief, background report to study by ICIS and MERIT for MNP-4, 2000. *Transitions and transition management*. Enschede: UT, Maastricht: MERIT.

Giddens, A., 1984. *The Constitution of Society. Outline of the Theory of Structuration*. Berkeley and Los Angeles: University of California Press.

Haertjens, E., 2014. *Projekt Milde Meetjes*. [pdf]. Ghent: Province of East Flanders. Available at: <http://www.oost-vlaanderen.be/docs/nl/bi/130852014%2012%2018%20voorstelling%20milde%20 meetjes%20%20-%20slotevent%20definitief.pdf> [Accessed 7 November 2017].

Hall, P. A. and Taylor, R. C. R., 1996. Political Science and the Three New Institutionalisms. *Political Studies* (1996), XLIV, pp. 936-957.

Hamedinger, A. and Dumke, H., 2013. Energie im urbanen Raum: Empirische Zwischenergebnisse des Governance-Moduls (Projekt ENUR). In: Bröthaler, J., Getzner, M., Giffinger, R., Hamedinger A., and Voigt, A., eds., 2013. *Jahrbuch des Departments für Raumplanung der TU Wien*, 2013, pp. 21-34. Vienna: Technical University of Vienna.

Healey, P., 1997. *Collaborative Planning, Shaping Places in Fragmented Societies*. Basingstoke and New York: Palgrave Macmillan.

Healey, P., 2004. Creativity and urban Governance. *Policy Studies*, Vol. 25(2), pp. 101-123.

Healey, P., 2006. *Collaborative Planning, Shaping Places in Fragmented Societies*. 2nd ed., Basingstoke and New York: Palgrave Macmillan.

Held, A., Ragwitz, M., Gephart, M., de Visser, E., Klessmann, C., 2014. *Design features of support schemes for renewable electricity*. Utrecht: Ecofys.

International Energy Agency (IEA), 2016. *Energy Policies of IEA Countries, Belgium 2016 Review*. [pdf] Paris: International Energy Agency. Available at:

<https://www.iea.org/publications/freepublications/publication/Energy\_Policies\_of\_IEA\_Countries\_Bel gium\_2016\_Review.pdf> [Accessed 26 September 2017].

ODE Flemish organisation for sustainable energy, 2017a. *Jaaroverzicht projectadviezen Windwerkgroep, maandag 06 november 2017.* [online] Available at: <https://www.ode.be/ode/publicaties/nieuwsbrief/14-windenergie/484-jaaroverzicht-projectadviezenwindwerkgroep> [Accessed 31 August 2017].

ODE Flemish organisation for sustainable energy, 2017b. *ODE.* [online] Available at: <https://www.ode.be/ode/ode> [Accessed 6 November 2017].

<http://dx.doi.org/10.1787/9789264268579-en> [Accessed 6 September 2017]. OECD Organisation for Economic Co-operation and Development, 2018. *Glossary of statistical terms*

[online]. Available at: <https://stats.oecd.org/glossary/detail.asp?ID=285> [Accessed 6 January 2018]. Office of the State Government of Burgenland, 2012. *Landsentwicklungsprogramm Burgenland – LEP 2011.* Eisenstadt: Office of the State Government of Burgenland.

Office of the State Government of Lower Austria, 2011. *Lower Austria Energy Roadmap 2030, Short Version.* [pdf] St. Pölten: Office of the State Government of Lower Austria. Available at: <http://www.noe.gv.at/noe/Energie/NOE\_Energiefahrplan\_2030\_Kurzfassung\_en.pdf> [Accessed 3 November 2017].

noe.at/fileadmin/root\_raumordnung/land/landesentwicklungsplanung/ROP\_Windkraft/Erl%C3%A4uter ungen\_ROP\_Windkraft.pdf> [Accessed 28 August 2017].

Oxford Dictionaries, 2017. *Free English dictionary.* [online]. Oxford: Oxford University Press. Available at: <https://en.oxforddictionaries.com/> [Accessed 20 November 2017].

Polski, M. M. and Ostrom, E., 1999. *An Institutional Framework for Policy Analysis and Design*. Working Paper W98-27, Workshop in Political Theory and Political Analysis, Indiana University, June 15.

holland.nl/Structuurvisie/geconsolideerde\_versie/20110223/d\_NL.IMRO.9928.DOSx2007x0002943SV-GC01.html> [Accessed 13 October 2017].

<http://www.rescoopv.be/sites/default/files/20140224\_Brief\_Ecopower\_en\_Beauvent\_- \_uittrede\_uit\_VWEA.pdf> [Accessed 9 September 2017].

Schöne, M. B., 2007. *Windturbines in het Landschap. Nieuw plaatsingsbeleid op basis van landschapsbeleving gewenst voor de jongste generatie windturbines*. Wageningen: Alterra. Available at: <http://edepot.wur.nl/32203> [Accessed 8 November 2017].

Sijmons, D., Hugtenburg, J., Feddes, F. and van Hoorn, A., eds., 2014. *Energy and Landscape. Designing Transition*. Rotterdam: nai010 publishers.

Szarka, J., 2007. *Wind Power in Europe. Politics, Business and Society*. Basingstoke: Palgrave Macmillan.

<http://www2.vlaanderen.be/economie/energiesparen/doc/Eindrapport\_draagvlakwindenergie.pdf> [Accessed 28 August 2017].

.

## Interviews, conversations, lectures and workshops

 Interviews, conversations, lectures and workshops (Actor dimension in brackets)

Interviews

Expert 19, manager (economy), 2016. Interviewed by the author. Rotterdam, 5 October 2016. Expert 20, pedagogue (economy), 2016. Interviewed by the author. Brussels, 28 October 2016.

Conversations

Expert 24, politics (politician). [conversation] guided tour of Munderfing wind park organised by the Technical University of Vienna and documented by the author. Munderfing, 17 September 2015.

#### Lectures

#### Workshops

Office of the State Government of Upper Austria, 2017. Reflexionsworkshop Dissertation Pia Nabielek. [workshop] organised by the author in collaboration with the Office of the State Government of Upper Austria (Directorate of Environment and Water Management) and documented by the author. Linz, 16 February 2017.

## Appendix

### A. Interview questions

#### 1. Position

*1.a Please describe your position, organisation and professional skills (education) related to*  [policy]*.*

#### 2. Conditions

*2.a What were the most important conditions/influencing factors that led to the* [policy]*?*

#### 3. Planning Arena

*3.a Who (persons/organisations at national/provincial/local levels) participated in the development of the* [policy] *and who had the power to take decisions? How did these parties come to decisions?*

*3.b Which communication format was used to work with these persons/organisations and what was* [your contribution/the contribution of other persons/organisations]*? Were there any conflicts?*

*3.c How intensive was* [your participation/the participation of other persons/organisations] *in the planning process for the* [policy]*?*

*3.d Which variations/choices were discussed during the development of the* [policy]*? E.g. spatial concepts such as clustering and dispersion, variations in formalizing zones for wind energy, landuse constraints and combinations.*

*3.e What knowledge was generated during the planning process [e.g. assessment of energy resources, surveys concerning social acceptance of wind energy]? Why was it necessary to produce information? How would you describe the quality of the information?*

#### 4. Planning Approach

*4.a What qualitative and quantitative criteria characterise the current planning approach to wind energy* [policy]*? Related to: energy goals, public support, landscape and environmental goals.*

*4.b Since when has the* [policy] *been implemented?*

#### 5. Outcome

*5.a How successful has the implementation of the* [policy] *been so far? What goals have been achieved? Related to: energy goals, public support, landscape and environmental goals.*

*5.b What factors have influenced the achievement of these goals in a positive/negative way (drivers and barriers)?*

*5.c Did the implementation process lead to an amendment of the* [policy]*? Do you expect an amendment/update of the* [policy] *in the coming years? Why?*

*5.d Is wind energy implementation being monitored and, if so, how does it work?*

## B. Documentation of case studies

#### B.1 Timeline of wind energy policies in South Holland

(Spatial-organisational level in brackets)

Before 2009

2001: First wind energy covenant Port of Rotterdam (micro) 2003: South Holland Wind Energy Policy Plan *Nota Wervel* (meso) 2008: Adoption of regional climate agenda by Rotterdam city region (micro)

Planning phase 1: 2009-2011

From general rules to a spatial-geographic planning approach 2009: Directive 2009/28/EC, National Renewable Energy Action Plan (macro) 2009: Amendment to Dutch Electricity Act (macro) 2009: Second wind energy covenant Port of Rotterdam (micro) 2011: South Holland Wind Energy Policy Plan *Nota Wervelender* (meso)

Planning phase 2: 2012-2014

Earmarking land for wind energy targets 2012: National Policy for Infrastructure and Spatial Planning (macro) 2012: Wind energy covenant Rotterdam City Region (micro) 2012: Wind energy covenant Goeree-Overflakkee (micro) 2013: Dutch Energy Agreement (macro) 2014: National Structure Plan for Onshore Wind Energy (macro) 2014: South Holland Structure Plan (meso)

#### B.2 Timeline of wind energy policies in Lower Austria

(Spatial-organisational level in brackets)

Before 2003 2002: Wind energy zones in Burgenland (meso)

Planning phase 1: 2003-2004

Creating generic distance rules

2003: (until 2008) Microregional schemes in selected parts of Lower Austria (micro) 2004: Distance regulation, Amendment to Lower Austrian Spatial Planning Act (meso) 2009: Directive 2009/28/EC, National Renewable Energy Action Plan (macro) 2011: ÖREK Spatial Development Scheme of the Austrian Conference on Spatial Planning (macro) 2011: Lower Austria Energy Roadmap (meso) 2012: Green Electricity Act (macro)

Planning phase 2: 2013-2014

Earmarking land for wind energy targets

2014: Sek ROP Lower Austrian sectoral spatial planning ordinance for wind energy (meso)

#### B.3 Timeline of wind energy policies in East Flanders

(Spatial-organisational level in brackets)

Before 2007 1997: Flemish spatial structure plan (macro) 2000: First wind letter by the Flemish government (macro) 2003: (until 2009) GRUPs Regional implementation plans for wind energy in Flanders (macro) 2005: East Flanders environmental policy plan (meso) 2006: Second circular letter on wind energy (macro) Planning phase 1: 2007-2009 From general rules to implementation areas 2009: Directive 2009/28/EC, National Renewable Energy Action Plan (macro) 2009: East Flanders spatial policy plan for wind energy (*Addendum aan het PRS: Provinciaal Beleidskader Windturbines*) (meso) 2009: Flemish energy vision *Vlaanderen in Actie* (macro) 2009: Amendment to Flemish Spatial Planning Act (*clichering*) (macro)

Planning phase 2: 2010-2014

Earmarking land for wind energy

2014: East Flanders Implementation Plans for wind energy in the Maldegem-Eeklo and E40- Aalter-Aalst areas (meso)

#### B.4 Documentation interview statements desired and undesired effects

Table 22. Longlist of desired and undesired effects of planning choices in South Holland, Lower Austria and East Flanders mentioned by interviewed experts

x observed effect

(x) effect expected in the opinion of interviewed experts

## C. Documentation of workshop results

Table 23. Workshop results concerning the evaluation of the transferability (rather high, moderate, rather low) of drivers identified in three case studies

Appendix

214

Delivering sustainable energy solutions has become a fundamental task of spatial planning. This doctoral thesis considers the field of tension between higher-tier energy schemes and local-level implementation practices by analysing regional planning policies regarding wind power from an institutional perspective.

Institutional challenges in spatial planning are closely related in particular to the flexibility and adaptability of those planning practices that are needed to supply 'acceptable locations'. Similar trends can be detected at a European level: targeted energy values are combined with administratively defined spaces - by putting the zoning of wind energy generation on regional spatial planning agendas. The outlining of wind power zones is not merely a technical act that determines the territorial spread of wind turbines. Rather, it configures social- organisational entities in which regionally varying sets of actors interact and, in the best case, join forces.

Pia Nabielek

**WIND POWER DEPLOYMENT IN URBANISED REGIONS**


**3. Microstructure observation**

To see microstructure of Gr-MREs, LV-SEM (JSM 6490LV SEM) is used. Figures 1- 3 show the surface imaging for MRE microstructures. Specifically, Fig. 1 shows the microstructure of isotropic and anisotropic Gr-MREs without graphite. The carbonyl iron particles are arranged in chains in the anisotropic sample, where they are dispersed randomly in the isotropic sample. According to Fig. 2 (a) and Fig. 3 (a), in the anisotropic Gr-MREs, the carbonyl iron particles are arranged in chains, whereas the graphite powders dispersed randomly in the matrix. The reason of this phenomenon is that the magnetic field only affects the carbonyl iron particles, but not the graphite. So upon magnetisation, the carbonyl iron particle chains tend to orient along the same direction as the magnetic field in the matrix.

By comparing Fig. 1 (a), Fig. 2 (a) and Fig. 3 (ba), we can see that the carbonyl iron chains in the sample without graphite have the best alignment performance. Further, the carbonyl iron chains in Fig. 2 (a) are aligned better than those in Fig. 3 (a). The reason is that when the mixture of carbonyl iron, silicone rubber, silicone oil and graphite is curing under the magnetic field, the graphite powders in Gr-MREs affect the carbonyl iron particles' movement. The more graphite in the mixture, the more effects are applied on to the carbonyl iron chains, which influence the magnetorheology of MREs.

**Table 1.** Components of Gr MRE samples


**Meet the editor**

Prof. Dr. Bashir received his PhD in Electronics and Telecommunications Engineering, University of Bradford, West Yorkshire, in 1980/84. His research interests include antennas and radio wave propagation, optical communication systems, microwave and satellite systems, EM theory, and EM scattering computation methods; there is a significant amount of original publications

in these fields. An InTech book, *Electromagnetic Radiation*, edited by Prof. Bashir was first published in June 2012 (p. cm. ISBN 978-953-51-0639-5).


**5. Methodology**

Next, we establish the essential steps to apply the speaker walk technique 2.0, starting from the essential keys of the classic "loci" technique.

*Efficient Conscious Speaking - Live Communication Pedagogical Technique… DOI: http://dx.doi.org/10.5772/intechopen.101093*

and images, it will not be difficult for us to remember them [17]. In this way, the true essence of the method comes to light and acquires its maximum value when it allows us a pleasant liberation from the use of any role on stage [18]. Creative art of free, with full confidence and determination of the speaker in the present. Through our method we manage to automatically convert abstract or symbolic objects in information and spatial anchor for the speaker.


**4.2 Slope stability analysis (step 4** � **10)**

In the second section, and slope stability analysis using finite element model. The FOS is calculated by the stress analysis method (SAM) and the behavior up to the slope failure is analyzed by the nonlinear static analysis with*k*0 condition. The

#### **Table 1.**

*Physical parameters of the soil of slope applied to slope stability analysis.*

**Figure 3.** *Variation of the strength parameters of slope according to strength reduction factor.*

#### *Integrated Analysis Method for Stability Analysis and Maintenance of Cut-Slope in Urban DOI: http://dx.doi.org/10.5772/intechopen.94252*

displacements until the slope failure analyzed using the slope stability analysis plot the cumulative displacement curve, velocity curve, and inverse velocity curve and, applied to the maintenance methods of the slope.


*2.4.2 Beyond the state of the art*

In this proposal, we will advance the state of the art by designing algorithms for video-analysis, text mining or case-based reasoning that are scalable and can benefit from parallel processing for the computing and data intensive tasks. This will allow the system to deal with varying workloads for large organizations and provide analysis response times [48] in line with police investigation requirements.


**2. Epidemiology**

In Western countries the incidence of osteomyelitis and septic arthritis is 5-12 per 100.000 infants [3]. The overall incidence rate for bone and joint infections is 0.12 per 1000 live births and 0.67 per 1000 neonatal intensive care (NICU) admissions [4], with a mortality rate of 7.3% [5]. Some recent studies have reported an estimated incidence of 1-7 per 1000 hospital admissions for neonatal osteomyelitis [6,7]. In a review of more than 300 cases of neonatal osteomyelitis male infants are seen to predominate over females (1.6:1) and preterm infants to be at higher risk than term infants [8-10]. Risk factors for osteomyelitis and septic arthritis in preterm infants are mostly iatrogenic, including invasive procedures, intravenous or intra-arterial catheters, parenteral nutrition, ventilatory support, and bacteremia with nosocomial pathogens [11,12]. Two subgroups of neonates are affected: premature neonates with prolonged hospitalization and otherwise healthy newborns presenting within 2 to 4 weeks of discharge [13].


*3.1. Time Activity Patterns*

In Table 3, data on time-activity patterns of the children under investigation are reported, which were obtained from the activity diaries filled in by children and parents during the measurements. The median data demonstrate that children spend the most significant time fraction performing indoor activities in indoor microenvironments: indeed, the median time spent by the children indoor, as sum of the microenvironments labelled as "sleeping", "indoor day", "cooking & eating", resulted equal to 68–69%, to which must be added the time spent at school (25%). On the contrary, the time fraction spent in "outdoor day" (2–3%) and "transport" (3–4%) microenvironments resulted very limited, likely due to the fact that just school days were included in the experimental analysis, thus, the time spent in "transport" microenvironment is mostly limited to the time to take children to school. The huge time spent in indoor environments is consistent with our previous studies analyzing western populations, in which emerged that also adults spend a significant time fraction (roughly 90%)

performing indoor activities [53,62,63]. Amongst the indoor activities, the time spent in "cooking & eating" microenvironment (here 8%) is of particular concern since these activities were recognized in our previous papers as the most influencing in terms of exposure and health risk [36,89].

**Table 3.** Time activity pattern, particle concentrations (PN and LDSA) and dose received by children of the three schools in the different microenvironments expressed as median values and range (5th and 95th percentile). Total daily doses as sum of the median doses received in the different microenvironments are also reported as well as daily dose fractions and intensity–dose ratios.


**Author details**

Žarko M. Ilin1 and Dubravka M. Savić2 \*

1 Department for Field and Vegetable Crops, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia

2 Department for Farming and Vegetable Crop Science, Faculty of Agriculture, University of Belgrade, Belgrade, Serbia

\*Address all correspondence to<EMAIL_ADDRESS><EMAIL_ADDRESS>
© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.