bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-internal variable thermodynamics modelling of severe plastic deformation: Dislocation and flow stress evolutions
Authors: Parvin H. , Kazeminezhad M.
Published: January 2015

Two-internal variable thermodynamics model is presented to investigate the evolution of microstructure and flow stress during severe plastic deformation. Previous studies have shown that due to heterogeneous distribution of dislocations during severe plastic deformation, the use of multivariable models is needed. In this regard, a two-internal variable model is presented. In the present paper, the dislocation densities in the subgrain boundaries and interiors are considered as internal variables. The model uses general laws of thermodynamics and describes the evolution of the dislocation densities on the basis of parameters such as the self-diffusion activation energy and the stacking fault energy. The model predicts the dislocation density, subgrain size and strength. To verify the model, the achieved results are compared with the experimental data.
Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?
Authors: Udy Andrew A , Lipman Jeffrey , Jarrett Paul , Klein Kerenaftali , Wallis Steven C , Patel Kashyap , Kirkpatrick Carl MJ , Kruger Peter S , Paterson David L , Roberts Michael S , Roberts Jason A
Published: January 2015

Introduction

The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing.

Methods

To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values.

Results

In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures.

Conclusions

Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.
Influence of the route of exposure and the matrix on the sensitisation potency of a major cows’ milk allergen
Authors: Wavrin Sophie , Bernard Herve , Wal Jean‐Michel , Adel‐Patient Karine
Published: January 2015

Background

Allergic sensitisation to food may occur through non‐gastrointestinal routes such as via skin or lung. We recently demonstrated in mice that cutaneous or respiratory pre‐exposures to peanut proteins on intact epithelia induce a Th2 priming and allow subsequent oral sensitization without the use of adjuvant. We then aimed to assess the impact of a similar pattern of exposure to another relevant food allergen, cows’ milk.

Findings

The humoral and cellular immune response induced in BALB/cJ mice after repeated cutaneous applications on intact skin or after intranasal administration of cows’ milk proteins was analysed. In order to assess the potential effect of the food matrix, we used either a purified major cows’ milk allergen, β‐lactoglobulin (BLG), or whole cows’ milk containing the same amount of BLG. We then studied the impact of these pre‐exposures on a subsequent oral exposure to milk in the presence or absence of the mucosal Th2 adjuvant, Cholera toxin (CT). Cutaneous applications of milk induced production of BLG‐specific IgE and IgG1 in 5 and 8 mice out of 20 respectively, whereas purified BLG alone did not. Intranasal exposure to milk, but not to BLG, led to BLG‐specific IgG1 production in 8 out of 20 mice. Notably, cutaneous pre‐exposure to milk favours further oral sensitisation without CT, while intra‐nasal pre‐exposure to BLG prevents further experimental sensitisation.

Conclusions

Altogether, our results thus demonstrated that the immune response induced after non‐gastrointestinal exposure to food depends on the allergen, the matrix and the route of exposure.
Multivariate empirical mode decomposition based sub-frequency bands analysis of the default mode network: a resting-state fMRI data study
Authors: Zhang Tao , Xu Peng , Guo Lanjin , Chen Rui , Zhang Rui , He Hui , Xie Qiankun , Liu Tiejun , Luo Cheng , Yao Dezhong
Published: January 2015

Resting-state functional connectivity reveals intrinsic, spontaneous networks that elucidate the functional architecture of the human brain. The default mode network (DMN) is the most important and stable intrinsic connectivity network (ICN), which involves several cognition functions, such as episodic memory and self-introspection. It has been suggested that low-frequency fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain and these low-frequency fluctuations correspond to functionally relevant resting-state networks. Several studies have revealed that the function of the brain is accomplished in certain low sub-frequency band. However, the concerned frequency bands are determined by experience, neglecting the intrinsic information of BOLD time series. In this study, we apply a full data-driven analysis, i.e., multivariate empirical mode decomposition (MEMD), to decompose resting-state fMRI data into the different sub-band DMNs, aiming to reveal the corresponding connectivity functions in separate sub-band DMN. Our results revealed that MEMD can adaptively decompose signals into intrinsic mode functions (IMFs) with the similar patterns across subjects. Furthermore, the sub-network constructed from the IMFs revealed that the different sub-band DMNs correspond to the different brain functional connectivity, inferring the possible relationships between sub-frequency band and cognitions. Owing to its data-driven merit, the proposed MEMD analysis may provide a new insight for fMRI-related studies.
Radiographic Progression-Free Survival As a Response Biomarker in Metastatic Castration-Resistant Prostate Cancer: COU-AA-302 Results
Authors: Morris Michael J. , Molina Arturo , Small Eric J. , de Bono Johann S. , Logothetis Christopher J. , Fizazi Karim , de Souza Paul , Kantoff Philip W. , Higano Celestia S. , Li Jinhui , Kheoh Thian , Larson Steven M. , Matheny Shannon L. , Naini Vahid , Burzykowski Tomasz , Griffin Thomas W. , Scher Howard I. , Ryan Charles J.
Published: January 2015

Purpose

Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC.

Patients and Methods

rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation.

Results

A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P < .001 and HR, 0.53; 95% CI, 0.45 to 0.62; P < .001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72.

Conclusion

rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials.
Development and Validation of a Nomogram for Predicting Survival in Patients With Resected Non–Small-Cell Lung Cancer
Authors: Liang Wenhua , Zhang Li , Jiang Gening , Wang Qun , Liu Lunxu , Liu Deruo , Wang Zheng , Zhu Zhihua , Deng Qiuhua , Xiong Xinguo , Shao Wenlong , Shi Xiaoshun , He Jianxing
Published: January 2015

Purpose

A nomogram is a useful and convenient tool for individualized cancer prognoses. We sought to develop a clinical nomogram for predicting survival of patients with resected non–small-cell lung cancer (NSCLC).

Patients and Methods

On the basis of data from a multi-institutional registry of 6,111 patients with resected NSCLC in China, we identified and integrated significant prognostic factors for survival to build a nomogram. The model was subjected to bootstrap internal validation and to external validation with a separate cohort of 2,148 patients from the International Association for the Study of Lung Cancer (IASLC) database. The predictive accuracy and discriminative ability were measured by concordance index (C-index) and risk group stratification.

Results

A total of 5,261 patients were included for analysis. Six independent prognostic factors were identified and entered into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year overall survival (OS) showed optimal agreement between nomogram prediction and actual observation. The C-index of the nomogram was higher than that of the seventh edition American Joint Committee on Cancer TNM staging system for predicting OS (primary cohort, 0.71 v 0.68, respectively; P < .01; IASLC cohort, 0.67 v 0.64, respectively; P = .06). The stratification into different risk groups allowed significant distinction between survival curves within respective TNM categories.

Conclusion

We established and validated a novel nomogram that can provide individual prediction of OS for patients with resected NSCLC. This practical prognostic model may help clinicians in decision making and design of clinical studies.
Transfer of Communication Skills to the Workplace: Impact of a 38-Hour Communication Skills Training Program Designed for Radiotherapy Teams
Authors: Merckaert Isabelle , Delevallez France , Gibon Anne-Sophie , Liénard Aurore , Libert Yves , Delvaux Nicole , Marchal Serge , Etienne Anne-Marie , Bragard Isabelle , Reynaert Christine , Slachmuylder Jean-Louis , Scalliet Pierre , Van Houtte Paul , Coucke Philippe , Razavi Darius
Published: January 2015

Purpose

This study assessed the efficacy of a 38-hour communication skills training program designed to train a multidisciplinary radiotherapy team.

Methods

Four radiotherapy teams were randomly assigned to a training program or a waiting list. Assessments were scheduled at baseline and after training for the training group and at baseline and 4 months later for the waiting list group. Assessments included an audio recording of a radiotherapy planning session to assess team members' communication skills and expression of concerns of patients with breast cancer (analyzed with content analysis software) and an adapted European Organisation for Research and Treatment of Cancer satisfaction with care questionnaire completed by patients at the end of radiotherapy.

Results

Two hundred thirty-seven radiotherapy planning sessions were recorded. Compared with members of the untrained teams, members of the trained teams acquired, over time, more assessment skills (P = .003) and more supportive skills (P = .050) and provided more setting information (P = .010). Over time, patients interacting with members of the trained teams asked more open questions (P = .022), expressed more emotional words (P = .025), and exhibited a higher satisfaction level regarding nurses' interventions (P = .028).

Conclusion

The 38-hour training program facilitated transfer of team member learned communication skills to the clinical practice and improved patients' satisfaction with care.
Phase II Study of Everolimus and Letrozole in Patients With Recurrent Endometrial Carcinoma
Authors: Slomovitz Brian M. , Jiang Yunyun , Yates Melinda S. , Soliman Pamela T. , Johnston Taren , Nowakowski Maureen , Levenback Charles , Zhang Qian , Ring Kari , Munsell Mark F. , Gershenson David M. , Lu Karen H. , Coleman Robert L.
Published: January 2015

Purpose

The phosphoinositol-3 kinase (PI3K) pathway is frequently dysregulated in endometrial cancer (EC). Hormonal manipulation leads to response in some patients with EC, but resistance derived from PI3K pathway activation has been documented. Targeting mammalian target of rapamycin (mTOR) may overcome endocrine resistance. We conducted a two-institution phase II trial of everolimus and letrozole in women with recurrent EC.

Patients and Methods

Patients were considered incurable, had measurable disease, and were treated with up to two prior cytotoxic regimens. Everolimus was administered orally at 10 mg daily and letrozole was administered orally at 2.5 mg daily. Each cycle consisted of 4 weeks of therapy. Patients were treated until progression, toxicity, or complete response (CR). The primary end point was the clinical benefit rate (CBR), which was defined as CR, partial response, or stable disease (≥ 16 weeks) by RECIST 1.0 criteria. Translational studies were performed to correlate biomarkers with response.

Results

Thirty-eight patients were enrolled (median age, 62 years; range, 24 to 82 years). Thirty-five patients were evaluable for response. The CBR was 40% (14 of 35 patients); the median number of cycles among responders was 15 (range, seven to 29 cycles). The confirmed objective response rate (RR) was 32% (11 of 35 patients; nine CRs and two partial responses; median, 15 cycles; range, eight to 29 cycles). Twenty percent of patients (seven of 35 patients) were taken off treatment after a prolonged CR and at the discretion of the treating clinician. None of the patients discontinued treatment as a result of toxicity. Serous histology was the best predictor of lack of response. Patients with endometrioid histology and CTNNB1 mutations responded well to everolimus and letrozole.

Conclusion

Everolimus plus letrozole results in a high CBR and RR in patients with recurrent EC. Further development of this combination in recurrent endometrioid EC is under way.
Myocardial and Cardiomyocyte Stress Resilience Is Enhanced in Aromatase-Deficient Female Mouse Hearts Through CaMKIIδ Activation
Authors: Bell James R. , Bernasochi Gabriel B. , Wollermann Amanda C. , Raaijmakers Antonia J. A. , Boon Wah Chin , Simpson Evan R. , Curl Claire L. , Mellor Kimberley M. , Delbridge Lea M. D.
Published: January 2015

The role of sex steroids in cardioprotection is contentious, with large clinical trials investigating hormone supplementation failing to deliver outcomes expected from observational studies. Mechanistic understanding of androgen/estrogen myocardial actions is lacking. Using a genetic model of aromatase tissue deficiency (ArKO) in female mice, the goal of this investigation was to evaluate the capacity of a shift in cardiac endogenous steroid conversion to influence ischemia-reperfusion resilience by optimizing cardiomyocyte Ca2+ handling responses. In isolated normoxic cardiomyocytes, basal Ca2+ transient amplitude and extent of shortening were greater in ArKO myocytes, with preservation of diastolic Ca2+ levels. Isolated ArKO cardiomyocytes exposed to a high Ca2+ load exhibited greater Ca2+ transient and contractile amplitudes, associated with a greater postrest spontaneous sarcoplasmic reticulum Ca2+ load-release. Microarray differential gene expression analysis of normoxic ventricular tissues from ArKO vs wild-type identified a significant influence of aromatase on genes involved in cardiac Ca2+ handling and signaling [including calmodulin dependent kinase II (CaMKII)-δ], myofilament structure and function, glucose uptake and signaling, and enzymes controlling phosphorylation-specific posttranslational modification status. CaMKII expression was not changed in ventricular tissues, although CaMKIIδ activation and phosphorylation of downstream targets was enhanced in ArKO hearts subjected to ischemia-reperfusion. Overall, this investigation shows that relative withdrawal of estrogen in favor of testosterone through genetically induced tissue aromatase deficiency in females modifies the gene expression profile to effect inotropic support via optimized Ca2+ handling in response to stress, with a modest impact on basal function. Consideration of aromatase inhibition, acutely or chronically, may have a role in cardioprotection, of particular relevance to women.
Disruption of Insulin Signaling in Myf5-Expressing Progenitors Leads to Marked Paucity of Brown Fat but Normal Muscle Development
Authors: Lynes Matthew D. , Schulz Tim J. , Pan Andrew J. , Tseng Yu-Hua
Published: January 2015

Insulin exerts pleiotropic effects on cell growth, survival, and metabolism, and its role in multiple tissues has been dissected using conditional knockout mice; however, its role in development has not been studied. Lineage tracing experiments have demonstrated that interscapular brown adipose tissue (BAT) arises from a Myf5-positive lineage shared with skeletal muscle and distinct from the majority of white adipose tissue (WAT) precursors. In this study, we sought to investigate the effects of impaired insulin signaling in the Myf5-expressing precursor cells by deleting the insulin receptor gene. Mice lacking insulin receptor in the Myf5 lineage (Myf5IRKO) have a decrease of interscapular BAT mass; however, muscle development appeared normal. Histologically, the residual BAT had decreased cell size but appeared mature and potentially functional. Expression of adipogenic inhibitors preadipocyte factor-1, Necdin, and wingless-type MMTV integration site member 10a in the residual BAT tissue was nonetheless increased compared with controls, and there was an enrichment of progenitor cells with impaired adipogenic differentiation capacity, suggesting a suppression of adipogenesis in BAT. Surprisingly, when cold challenged, Myf5IRKO mice did not show impaired thermogenesis. This resistance to cold could be attributed to an increased presence of uncoupling protein 1-positive brown adipocytes in sc WAT as well as increased expression of lipolytic activity in BAT. These data suggest a critical role of insulin signaling in the development of interscapular BAT from Myf5-positive progenitor cells, but it appears to be dispensable for muscle development. They also underscore the importance of compensatory browning of sc WAT in the absence of BAT for thermoregulation.
A Modest Proposal
Authors: Schneider Bethany
Published: January 2015

Laura Ingalls Wilder's Little House on the Prairie (1935) is a cannibal text. Zitkala-Ša's (Yankton-Nakota) essays “Impressions of an Indian Childhood” and “The School Days of an Indian Girl” (1900) can be found in the guts of the settler-colonial children's novel. Practices of unacknowledged citation that we might usually see in literary works as intertextual jouissance, or in extreme cases as plagiarism, are best understood here as cannibal practice—the digestive making of two into one—by Wilder and her collaborator and daughter, Rose Wilder Lane. Zitkala-Ša's autobiographical essays, which she wrote as an excoriating critique of assimilationist Indian boarding schools, are consumed by the settler writer and made to nourish Wilder's famously blank and generic Midwest. Zitkala-Ša's time and place—the bloodily contested land of South Dakota of the 1880s—can be found incorporated into the fantastically pure and bloodless 1870 Kansas of Wilder's fantasy.
Longevity of Atlantic Sharpnose Sharks Rhizoprionodon terraenovae and Blacknose Sharks Carcharhinus acronotus in the western North Atlantic Ocean based on tag-recapture data and direct age estimates
Authors: Frazier Bryan S. , Driggers III William B. , Ulrich Glenn F.
Published: January 2015

Longevity of Rhizoprionodon terraenovae and Carcharhinus acronotus in the western North Atlantic Ocean was examined using direct age estimates from vertebral sections and tag-recapture data. Time-at-liberty ranged from 7.7-14.0 years (mean =10.1) for R. terraenovae and 10.9-12.8 years (mean =11.9) for C. acronotus. Maximum estimated longevity was determined to be 19.8 years through tag-recapture data and 18.5 years from direct age estimates for R. terraenovae and 22.8 years through tag-recapture data and 20.5 years through direct age estimates for C. acronotus. These longevity estimates represent a large increase over previous estimates and may have significant effects on analyses that depend on longevity including lifetime fecundity, mortality rates, demographic analyses and stock assessments.
Do Insurers Compete on the Federal Health Insurance Exchange?
Authors: Cohen Jesse N. , Coppock Alexander , Ghosh Arnab K. , Geisler Benjamin P.
Published: January 2015

Background: On the U.S. Federal Health Insurance Exchange established by the Affordable Care Act, states with fewer insurers have higher insurance premiums than states with more insurers. This expected feature of a competitive market has not been studied within states, however. We tested the hypothesis that insurance premiums decrease in more competitive geographic rating areas within states in the U.S.A.

Methodology/principle findings: This cross-sectional study utilized publicly available premiums from the Federal Health Insurance Exchange website, www.healthcare.gov. Univariate and multivariate analyses were used to model premiums based on the number of insurers in geographic rating areas. The relationship between premiums and the number of insurers competing in a geographic rating area was also calculated for each unique insurance plan offered on the exchange. The data set and statistical code used for this research is linked in the publication. We found that there was an unexpected, marginally positive relationship between average monthly premiums and the number of insurers in a geographic rating area (+$5.71 in monthly premiums per additional insurer, p<0.001). We also found that identical plans tend to be offered with marginally higher premiums in rating areas with more insurers (+$3.18 in monthly premiums per additional insurer, p=0.002), contrary to the relationship we expected from a competitive marketplace. The principle limitation of the study is that this unexpected relationship, which suggests a lack of competitiveness of this early market, could be due to unobserved confounding factors that influence pricing in more competitive rating areas.

Conclusion: On the Federal Health Insurance Exchange, the price of insurance is higher in more competitive rating areas within states. This may be explained by lack of competition in this early stage market.
Avascular necrosis as a complication of the treatment of dislocation of the hip in children with cerebral palsy
Authors: Koch A. , Jozwiak M. , Idzior M. , Molinska-Glura M. , Szulc A.
Published: January 2015

We investigated the incidence and risk factors for the development of avascular necrosis (AVN) of the femoral head in the course of treatment of children with cerebral palsy (CP) and dislocation of the hip. All underwent open reduction, proximal femoral and Dega pelvic osteotomy. The inclusion criteria were: a predominantly spastic form of CP, dislocation of the hip (migration percentage, MP > 80%), Gross Motor Function Classification System, (GMFCS) grade IV to V, a primary surgical procedure and follow-up of > one year.

There were 81 consecutive children (40 girls and 41 boys) in the study. Their mean age was nine years (3.5 to 13.8) and mean follow-up was 5.5 years (1.6 to 15.1). Radiological evaluation included measurement of the MP, the acetabular index (AI), the epiphyseal shaft angle (ESA) and the pelvic femoral angle (PFA). The presence and grade of AVN were assessed radiologically according to the Kruczynski classification.

Signs of AVN (grades I to V) were seen in 79 hips (68.7%). A total of 23 hips (18%) were classified between grades III and V.

Although open reduction of the hip combined with femoral and Dega osteotomy is an effective form of treatment for children with CP and dislocation of the hip, there were signs of avascular necrosis in about two-thirds of the children. There was a strong correlation between post-operative pain and the severity of the grade of AVN.

Cite this article: Bone Joint J 2015;97-B:270–6.
Iatrogenic popliteal artery injury in non arthroplasty knee surgery
Authors: Bernhoff K. , Björck M.
Published: January 2015

We have investigated iatrogenic popliteal artery injuries (PAI) during non arthroplasty knee surgery regarding mechanism of injury, treatment and outcomes, and to identify successful strategies when injury occurs.

In all, 21 iatrogenic popliteal artery injuries in 21 patients during knee surgery other than knee arthroplasty were identified from the Swedish Vascular Registry (Swedvasc) between 1987 and 2011. Prospective registry data were supplemented with case-records, including long-term follow-up. In total, 13 patients suffered PAI during elective surgery and eight during urgent surgery such as fracture fixation or tumour resection. Nine injuries were detected intra-operatively, five within 12 to 48 hours and seven > 48 hours post-operatively (two days to 23 years).

There were 19 open vascular and two endovascular surgical repairs. Two patients died within six months of surgery. One patient required amputation. Only six patients had a complete recovery of whom had the vascular injury detected at time of injury and repaired by a vascular surgeon. Patients sustaining vascular injury during elective procedures are more likely to litigate (p = 0.029).

We conclude that outcomes are poorer when there is a delay of diagnosis and treatment, and that orthopaedic surgeons should develop strategies to detect PAI early and ensure rapid access to vascular surgical support.

Cite this article: Bone Joint J 2015;97-B:192–6.
Synovial C-reactive protein as a marker for chronic periprosthetic infection in total hip arthroplasty
Authors: Omar M. , Ettinger M. , Reichling M. , Petri M. , Guenther D. , Gehrke T. , Krettek C. , Mommsen P.
Published: January 2015

The aim of this study was to assess the role of synovial C-reactive protein (CRP) in the diagnosis of chronic periprosthetic hip infection. We prospectively collected synovial fluid from 89 patients undergoing revision hip arthroplasty and measured synovial CRP, serum CRP, erythrocyte sedimentation rate (ESR), synovial white blood cell (WBC) count and synovial percentages of polymorphonuclear neutrophils (PMN). Patients were classified as septic or aseptic by means of clinical, microbiological, serum and synovial fluid findings. The high viscosity of the synovial fluid precluded the analyses in nine patients permitting the results in 80 patients to be studied. There was a significant difference in synovial CRP levels between the septic (n = 21) and the aseptic (n = 59) cohort. According to the receiver operating characteristic curve, a synovial CRP threshold of 2.5 mg/l had a sensitivity of 95.5% and specificity of 93.3%. The area under the curve was 0.96. Compared with serum CRP and ESR, synovial CRP showed a high diagnostic value. According to these preliminary results, synovial CRP may be a useful parameter in diagnosing chronic periprosthetic hip infection.

Cite this article: Bone Joint J 2015; 97-B:173–6.
Neonatal clinical screening of the hip in the diagnosis of developmental dysplasia of the hip
Authors: Mace J. , Paton R. W.
Published: January 2015

Over a 15-year prospective period, 201 infants with a clinically unstable hip at neonatal screening were subsequently reviewed in a ‘one stop’ clinic where they were assessed clinically and sonographically. Their mean age was 1.62 weeks (95% confidence interval (CI) 1.35 to 1.89). Clinical neonatal hip screening revealed a sensitivity of 62% (mean, 62.6 95%CI 50.9 to 74.3), specificity of 99.8% (mean, 99.8, 95% CI 99.7 to 99.8) and positive predictive value (PPV) of 24% (mean, 26.2, 95% CI 19.3 to 33.0). Static and dynamic sonography for Graf type IV dysplastic hips had a 15-year sensitivity of 77% (mean, 75.8 95% CI 66.9 to 84.6), specificity of 99.8% (mean, 99.8, 95% CI 99.8 to 99.8) and a PPV of 49% (mean, 55.1, 95% CI 41.6 to 68.5). There were 36 infants with an irreducible dislocation of the hip (0.57 per 1000 live births), including six that failed to resolve with neonatal splintage.

Most clinically unstable hips referred to a specialist clinic are female and stabilise spontaneously. Most irreducible dislocations are not identified from this neonatal instability group. There may be a small subgroup of females with instability of the hip which may be at risk of progression to irreducibility despite early treatment in a Pavlik harness.

A controlled study is required to assess the value of neonatal clinical screening programmes.

Cite this article: Bone Joint J 2015;97-B:265-9.
Surgery for the correction of hallux valgus
Authors: Chong A. , Nazarian N. , Chandrananth J. , Tacey M. , Shepherd D. , Tran P.
Published: January 2015

This study sought to determine the medium-term patient-reported and radiographic outcomes in patients undergoing surgery for hallux valgus. A total of 118 patients (162 feet) underwent surgery for hallux valgus between January 2008 and June 2009. The Manchester-Oxford Foot Questionnaire (MOXFQ), a validated tool for the assessment of outcome after surgery for hallux valgus, was used and patient satisfaction was sought. The medical records and radiographs were reviewed retrospectively. At a mean of 5.2 years (4.7 to 6.0) post-operatively, the median combined MOXFQ score was 7.8 (IQR:0 to 32.8). The median domain scores for pain, walking/standing, and social interaction were 10 (IQR: 0 to 45), 0 (IQR: 0 to 32.1) and 6.3 (IQR: 0 to 25) respectively. A total of 119 procedures (73.9%, in 90 patients) were reported as satisfactory but only 53 feet (32.7%, in 43 patients) were completely asymptomatic. The mean (SD) correction of hallux valgus, intermetatarsal, and distal metatarsal articular angles was 18.5° (8.8°), 5.7° (3.3°), and 16.6° (8.8°), respectively. Multivariable regression analysis identified that an American Association of Anesthesiologists grade of > 1 (Incident Rate Ratio (IRR) = 1.67, p-value = 0.011) and recurrent deformity (IRR = 1.77, p-value = 0.003) were associated with significantly worse MOXFQ scores. No correlation was found between the severity of deformity, the type, or degree of surgical correction and the outcome. When using a validated outcome score for the assessment of outcome after surgery for hallux valgus, the long-term results are worse than expected when compared with the short- and mid-term outcomes, with 25.9% of patients dissatisfied at a mean follow-up of 5.2 years.

Cite this article: Bone Joint J 2015;97-B:208–14.
Inactivation of micro-organisms isolated from infected lower limb arthroplasties using high-intensity narrow-spectrum (HINS) light
Authors: Gupta S. , Maclean M. , Anderson J. G. , MacGregor S. J. , Meek R. M. D. , Grant M. H.
Published: January 2015

High-intensity narrow-spectrum (HINS) light is a novel violet-blue light inactivation technology which kills bacteria through a photodynamic process, and has been shown to have bactericidal activity against a wide range of species. Specimens from patients with infected hip and knee arthroplasties were collected over a one-year period (1 May 2009 to 30 April 2010). A range of these microbial isolates were tested for sensitivity to HINS-light. During testing, suspensions of the pathogens were exposed to increasing doses of HINS-light (of 123mW/cm2 irradiance). Non-light exposed control samples were also used. The samples were then plated onto agar plates and incubated at 37°C for 24 hours before enumeration. Complete inactivation (greater than 4-log10 reduction) was achieved for all of the isolates. The typical inactivation curve showed a slow initial reaction followed by a rapid period of inactivation. The doses of HINS-light required ranged between 118 and 2214 J/cm2. Gram-positive bacteria were generally found to be more susceptible than Gram-negative.

As HINS-light uses visible wavelengths, it can be safely used in the presence of patients and staff. This unique feature could lead to its possible use in the prevention of infection during surgery and post-operative dressing changes.

Cite this article: Bone Joint J 2015;97-B:283–8.
Clinical Actionability Enhanced through Deep Targeted Sequencing of Solid Tumors
Authors: Chen Ken , Meric-Bernstam Funda , Zhao Hao , Zhang Qingxiu , Ezzeddine Nader , Tang Lin-ya , Qi Yuan , Mao Yong , Chen Tenghui , Chong Zechen , Zhou Wanding , Zheng Xiaofeng , Johnson Amber , Aldape Kenneth D , Routbort Mark J , Luthra Rajyalakshmi , Kopetz Scott , Davies Michael A , de Groot John , Moulder Stacy , Vinod Ravi , Farhangfar Carol J , Shaw Kenna Mills , Mendelsohn John , Mills Gordon B , Karina Eterovic Agda
Published: January 2015

BACKGROUND

Further advances of targeted cancer therapy require comprehensive in-depth profiling of somatic mutations that are present in subpopulations of tumor cells in a clinical tumor sample. However, it is unclear to what extent such intratumor heterogeneity is present and whether it may affect clinical decision-making. To study this question, we established a deep targeted sequencing platform to identify potentially actionable DNA alterations in tumor samples.

METHODS

We assayed 515 formalin-fixed paraffin-embedded (FFPE) tumor samples and matched germline DNA (475 patients) from 11 disease sites by capturing and sequencing all the exons in 201 cancer-related genes. Mutations, indels, and copy number data were reported.

RESULTS

We obtained a 1000-fold mean sequencing depth and identified 4794 nonsynonymous mutations in the samples analyzed, of which 15.2% were present at <10% allele frequency. Most of these low level mutations occurred at known oncogenic hotspots and are likely functional. Identifying low level mutations improved identification of mutations in actionable genes in 118 (24.84%) patients, among which 47 (9.8%) otherwise would have been unactionable. In addition, acquiring ultrahigh depth also ensured a low false discovery rate (<2.2%) from FFPE samples.

CONCLUSIONS

Our results were as accurate as a commercially available CLIA-compliant hotspot panel but allowed the detection of a higher number of mutations in actionable genes. Our study reveals the critical importance of acquiring and utilizing high sequencing depth in profiling clinical tumor samples and presents a very useful platform for implementing routine sequencing in a cancer care institution.
Reviews Books
Authors: Collier Stuart , Zim Jason
Published: January 2015

Joe Dante, Nil Baskar and Gabe Klinger, eds., (2013), FilmmuseumSynemaPublikationen Vol. 19 Vienna: SYNEMA – Gesellschaft für Film und Medien, 256pp. (in English), ISBN: 9783901644528 (pbk), $32.50

The Music of James Bond, Jon Burlingame, (2012) New York: Oxford University Press, 304pp., ISBN: 9780199863303 (hbk), $35.00
Between the poles of Eisensteinian aesthetics: Editing patterns in Peter Watkins’ biographical films
Authors: Jovanovic Nenad
Published: January 2015

The ‘Brechtianisms’ of editing in Peter Watkins’ films have largely escaped critical attention, doubtless as a result of their medium-specific nature, whereby the links between those formal elements and Brecht – as primarily a stage practitioner – are obscured. This article employs the ideas of Sergei Mikhailovich Eisenstein, who shares Brecht’s indebtedness to Marxist dialectics and Russian formalism, to reveal and investigate both the convergences and divergences between the two artists and Watkins. I argue that Watkins’ biographic films Edvard Munch (1974) and Fritänkaren/The Freethinker (1994) illustrate the trajectory that has led Watkins from Eisensteinian montage of attractions to the Soviet practitioner and theorist’s intellectual montage as a dominant structural method. The article further points out that the strong affinities of The Freethinker’s formal operations with those of Brecht’s own works for the stage and screen are attributable broadly to the film’s refusal to subsume its stylistic unorthodoxies to the logic of psychological realism.
Ingmar Bergman, archivist
Authors: Holmberg Jan
Published: January 2015

In his autobiographical writings, Ingmar Bergman dismissed the value of collecting and saving materials from his personal and professional life. Yet he saved an enormous amount of personal and professional material, which was collected in a room in his island home on Fårö, Sweden. The material was transferred to the Swedish Film Institute and catalogued in the Ingmar Bergman Archives. The article suggests that Bergman’s archiving project served as a response to his own mortality, a theme also evident in his late films and autobiographical writings.
Reception material in the Ingmar Bergman Archives: Letters, essays, drawings
Authors: Hanssen Eirik Frisvold
Published: January 2015

This article considers documents relating to two different sections of the Ingmar Bergman Archives, emphasizing some of the social and cultural characteristics of the material. Analysis of letters from ordinary film spectators constitutes one portion. Another concerns Bergman’s employment as manager and director of the municipal children’s theatre Sagoteatern (The Fairy-Tale Theatre) in Stockholm (1941–1942). In both cases, the auteur archive becomes a site for examining the spectator rather than the auteur. The article examines how the chosen material may convey knowledge about spectatorship, and specific social and personal experiences of cinema and theatre, by making visible a range of cultural practices seldom associated with auteurism or ‘film art’, which nonetheless can be incorporated in an auteur archive.
Nordic practices and Nordic sensibilities in Finnish–Swedish co-productions: The case of Klaus Härö and Jarkko T. Laine
Authors: Bacon Henry
Published: January 2015

In Swedish and Danish cinema’s subtle variations of light, director Klaus Härö and cinematographer Jarkko Laine found initial inspiration for cinematic treatment of people in relation to their Nordic environment. While making their first three feature films in Sweden, the two Finns became acquainted with Swedish professional practices deriving from a long tradition of film-making. These differed in many ways from Finnish practices. While imposing certain limits, the Swedish system was also supportive in a way that the Finnish system was not. In Finland, a major break in tradition occurred following the fall of the studio system; there continues to be lower volume of film production. However, particularly in making their first two films Elina – som om jag inte fanns/Elina: As If I Wasn’t There (2002) and Äideistä parhain/Mother of Mine (2005) Härö and Laine were able to unite Finnish and Swedish creative talent and produce award-winning films.
Editorial: Metrology in surveying and mechanical engineering
Authors: Pospíšil Jiří
Published: January 2015

Introduction of a new bachelor study programme Metrology in curricula of Czech Technical University in Prague.
Measuring Repeatability of the Focus-variable Lenses
Authors: Řezníček Jan
Published: January 2015

In the field of photogrammetry, the optical system, usually represented by the glass lens, is used for metric purposes. Therefore, the aberration characteristics of such a lens, inducing deviations from projective imaging, has to be well known. However, the most important property of the metric lens is the stability of its glass and mechanical elements, ensuring long-term reliability of the measured parameters. In case of a focus-variable lens, the repeatability of the lens setup is important as well. Lenses with a fixed focal length are usually considered as “fixed” though, in fact, most of them contain one or more movable glass elements, providing the focusing function. In cases where the lens is not equipped with fixing screws, the repeatability of the calibration parameters should be known. This paper derives simple mathematical formulas that can be used for measuring the repeatability of the focus-variable lenses, and gives a demonstrative example of such measuring. The given procedure has the advantage that only demanded parameters are estimated, hence, no unwanted correlations with the additional parameters exist. The test arrangement enables us to measure each demanded magnification of the optical system, which is important in close-range photogrammetry.
Monitoring of a concrete roof using terrestrial laser scanning
Authors: Erdélyi Ján , Kopáčik Alojz , Ilkovičová Ľubica , Lipták Imrich , Kajánek Pavol
Published: January 2015

The paper deals with the geodetic monitoring of a parabolic shaped reinforced con-crete roof structure in the chemical company Duslo, Ltd. in Šaľa (Slovak Republic).The monitored structure is a part of the roof of a warehouse used for the storage offertilizer. The atmospheric conditions and the operation load caused deformationof the construction. For measurement was used the technology of terrestrial laserscanning. The displacements of the observed parts of the construction were cal-culated using planar surfaces by the procedure of Singular Value Decomposition ofmatrixes. The procedure of initial and 2 epochal measurements of deformations,the procedure of the data processing, and the results of the deformation monitoringare described.
Familial Mediterranean Fever
Authors: Kucuk Adem , Gezer Ilknur Albayrak , Ucar Ramazan , Karahan Ali Yavuz
Published: January 2015

Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.
Osteointegration of an Uncemented Modular Revision Stem Implanted during revision Hip Surgery
Authors: Šponer Pavel , Kučera Tomáš , Urban Karel , Zítko David , Diaz-Garcia Daniel , Grinac Michal
Published: January 2015

Background: Though mid-term survival rates of over 95% in several series have been published, there is still a paucity of related literature regarding the role of vertical stem instability in the osteointegration of fluted tapered stems. This paper presents a comprehensive and prospective assessment on short-term experiences with uncemented modular femoral stem in the treatment of defective femur during revision surgery of total hip replacement. Materials and methods: Clinical and radiological monitoring of 20 consecutive patients with implanted tapered fluted revision stem (Lima Corporate, Udine, Italy) was of 27 months in average (20–35 months). The average pre-operative Merle d’Aubigné and Postel method score was 6.3 points (3–10 points). The frequency of femur defects, classified according to Paprosky, was IIIA = 9 and IIIB = 11. Results: During last follow-up, the Merle d’Aubigné and Postel hip score was on average 11.7 (6–16 points). Compared to post-operation radiograph, stem migration of 1.9 mm (0–11 mm) on average was found. This vertical stem migration was observed only when comparing hip radiographs immediately after surgery, and at 6 weeks post-surgery. The Paprosky IIIA defects group, presented a subsided stem by an average of 1.5 mm. In the group of Paprosky IIIB defects, the stem subsidence was on average 2.3 mm. All 20 patients in the study showed excellent osteointegration of the uncemented revision modular stem. Conclusions: This study found and excellent osteointegration of the Lima uncemented tapered fluted revision modular stem in defective femur with a cortical bone segment present in the diaphyseal isthmus area. The initial vertical instability leading to stem migrating during the first six weeks following surgery did not, however, affect its osteointegration.
Investigation of Dose-Related Effects of Carnosine on Anxiety with Sympathetic Skin Response and T-maze
Authors: Dolu Nazan , Acer Hale , Kara Ali Yucel
Published: January 2015

Carnosine is a dipeptide formed of the amino acids β-alanine and histidine. Only a limited number of studies have examined the effects of carnosine on sympathetic nerve activation and anxiety. The present study was undertaken to determine the dose-related effects of carnosine on anxiety in the elevated T-maze test (ETM) with electrodermal activity (EDA). Carnosine was injected in three groups of rats with doses of 10 (low dose), 100 (medium dose) and 1000 (high dose) mg/kg i.p. Physiological saline was injected in the sham group. The anxiety scores of the rats were measured with ETM 20 minutes after injection. Then, SCL was measured. The decreased number of entries into the open arm (NEOA), the percentage of time spent in the open arm (% TSOA) and higher EDA [shown by skin conductance level (SCL)] indicate higher anxiety. The NEOA and % TSOA were lower in the high-dose group than in the other groups. SCL was lower in the medium-dose carnosine group than in the high-dose carnosine and sham groups. SCL was higher in the high-dose group than in the medium-dose and sham groups. Our results suggest that high-dose carnosine produced anxiety-like effects as assessed in the SCL and ETM. Medium-dose carnosine acted as an anxiolytic. The anxiety-related responses of carnosine depend on its dose-related effect.
Human Plasma and Human Platelet-rich Plasma as a Substitute for Fetal Calf Serum during Long-term Cultivation of Mesenchymal Dental Pulp Stem Cells
Authors: Suchánková Kleplová Tereza , Soukup Tomáš , Řeháček Vít , Suchánek Jakub
Published: January 2015

Aims: Our aims were to isolate and cultivate mesenchymal dental pulp stem cells (DPSC) in various media enriched with human blood components, and subsequently to investigate their basic biological properties. Methods: DPSC were cultivated in five different media based on α MEM containing different concentrations of human plasma (HP), platelet-rich plasma (PRP), or fetal calf serum (FCS). The DPSC biological properties were examined periodically. Results: We cultivated DPSC in the various cultivation media over 15 population doublings except for the medium supplemented with 10% HP. Our results showed that DPSC cultivated in medium supplemented with 10% PRP showed the shortest average population doubling time (DT) (28.6 ± 4.6 hours), in contrast to DPSC cultivated in 10% HP which indicated the longest DT (156.2 ± 17.8 hours); hence this part of the experiment had been cancelled in the 6th passage. DPSC cultivated in media with 2% FCS+ITS (DT 47.3 ± 10.4 hours), 2% PRP (DT 40.1 ± 5.7 hours) and 2% HP (DT 49.0 ± 15.2 hours) showed almost the same proliferative activity. DPSC’s viability in the 9th passage was over 90% except for the DPSC cultivated in the 10% HP media. Conclusions: We proved that human blood components are suitable substitution for FCS in cultivation media for long-term DPSC cultivation.