bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)
Authors: Dickler Maura N. , Barry William T. , Cirrincione Constance T. , Ellis Matthew J. , Moynahan Mary Ellen , Innocenti Federico , Hurria Arti , Rugo Hope S. , Lake Diana E. , Hahn Olwen , Schneider Bryan P. , Tripathy Debasish , Carey Lisa A. , Winer Eric P. , Hudis Clifford A. 
Published: May 2016

Purpose To investigate whether anti–vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor–positive metastatic breast cancer (MBC). Patients and Methods Women with hormone receptor–positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. Results From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). Conclusion The addition of bevacizumab to letrozole improved PFS in hormone receptor–positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting.
RGMB and neogenin control cell differentiation in the developing olfactory epithelium
Authors: Kam Joseph Wai Keung , Dumontier Emilie , Baim Christopher , Brignall Alexandra C. , Mendes da Silva David , Cowan Mitra , Kennedy Timothy E. , Cloutier Jean-François 
Published: May 2016

ABSTRACT
Cellular interactions are key for the differentiation of distinct cell types within developing epithelia, yet the molecular mechanisms engaged in these interactions remain poorly understood. In the developing olfactory epithelium (OE), neural stem/progenitor cells give rise to odorant-detecting olfactory receptor neurons (ORNs) and glial-like sustentacular (SUS) cells. Here, we show in mice that the transmembrane receptor neogenin (NEO1) and its membrane-bound ligand RGMB control the balance of neurons and glial cells produced in the OE. In this layered epithelium, neogenin is expressed in progenitor cells, while RGMB is restricted to adjacent newly born ORNs. Ablation of Rgmb via gene-targeting increases the number of dividing progenitor cells in the OE and leads to supernumerary SUS cells. Neogenin loss-of-function phenocopies these effects observed in Rgmb−/− mice, supporting the proposal that RGMB-neogenin signaling regulates progenitor cell numbers and SUS cell production. Interestingly, Neo1−/− mice also exhibit increased apoptosis of ORNs, implicating additional ligands in the neogenin-dependent survival of ORNs. Thus, our results indicate that RGMB-neogenin-mediated cell-cell interactions between newly born neurons and progenitor cells control the ratio of glia and neurons produced in the OE.
The natural defense system and the normative self model
Authors: Kourilsky Philippe 
Published: May 2016

Infectious agents are not the only agressors, and the immune system is not the sole defender of the organism. In an enlarged perspective, the ‘normative self model’ postulates that a ‘natural defense system’ protects man and other complex organisms against the environmental and internal hazards of life, including infections and cancers. It involves multiple error detection and correction mechanisms that confer robustness to the body at all levels of its organization. According to the model, the self relies on a set of physiological norms, and NONself (meaning : Non Obedient to the Norms of the self) is anything ‘off-norms’. The natural defense system comprises a set of ‘civil defenses’ (to which all cells in organs and tissues contribute), and a ‘professional army ‘, made of a smaller set of mobile cells. Mobile and non mobile cells differ in their tuning abilities. Tuning extends the recognition capabilities of NONself by the mobile cells, which increase their defensive function. To prevent them to drift, which would compromise self/NONself discrimination, the more plastic mobile cells need to periodically refer to the more stable non mobile cells to keep within physiological standards.
Private Equity and Industry Performance
Authors: Bernstein Shai , Lerner Josh , Sorensen Morten , Strömberg Per 
Published: May 2016

The growth of the private equity industry has spurred concerns about its impact on the economy. This analysis looks across nations and industries to assess the impact of private equity on industry performance. We find that industries where private equity funds invest grow more quickly in terms of total production and employment and appear less exposed to aggregate shocks. Our robustness tests provide some evidence that is consistent with our effects being driven by our preferred channel. This paper was accepted by Amit Seru, finance.
Tongue-tie division. Is it worth it? A retrospective cohort study
Authors: Braccio Serena , Chadderton Zoe , Sherridan Angela , Upadhyaya Manasvi 
Published: May 2016

Background: Breastfeeding is a complex process, influenced by various factors. Tongue tie may be an impediment to breastfeeding, so division of tongue tie (frenotomy) is routinely recommended to improve breastfeeding. Aims: This study aimed to assess the value of frenotomy based on its impact on breastfeeding-related problems. Methods: A 1-year retrospective cohort study was undertaken of all the patients referred to a London-based tongue-tie service with breastfeeding difficulties. A telephone survey was performed using a standardised questionnaire. Findings: The rate of exclusively breastfed babies increased from 36.7% before frenotomy to 53.8% at 48 hours post-procedure. All the breastfeeding-related problems significantly reduced by 48 hours post-procedure. There was no major bleeding, infection or ulceration reported. Of babies that had frenotomy, 3.2% underwent a second procedure. Conclusions: Frenotomy is a well-tolerated surgical procedure accompanied by very low complication rates. It significantly increases the exclusive breastfeeding rate in the short-term period and reduces breastfeeding-related problems.
Medium- and long-term results of high tibial osteotomy using Garches external fixator and gait analysis for dynamic correction in varus osteoarthritis of the knee
Authors: McClelland D. , Barlow D. , Moores T. S. , Wynn-Jones C. , Griffiths D. , Ogrodnik P. J. , Thomas P. B. M. 
Published: May 2016

In arthritis of the varus knee, a high tibial osteotomy (HTO) redistributes load from the diseased medial compartment to the unaffected lateral compartment.We report the outcome of 36 patients (33 men and three women) with 42 varus, arthritic knees who underwent HTO and dynamic correction using a Garches external fixator until they felt that normal alignment had been restored. The mean age of the patients was 54.11 years (34 to 68). Normal alignment was achieved at a mean 5.5 weeks (3 to 10) post-operatively. Radiographs, gait analysis and visual analogue scores for pain were measured pre- and post-operatively, at one year and at medium-term follow-up (mean six years; 2 to 10). Failure was defined as conversion to knee arthroplasty.Pre-operative gait analysis divided the 42 knees into two equal groups with high (17 patients) or low (19 patients) adductor moments. After correction, a statistically significant (p < 0.001, t-test,) change in adductor moment was achieved and maintained in both groups, with a rate of failure of three knees (7.1%), and 89% (95% confidence interval (CI) 84.9 to 94.7) survivorship at medium-term follow-up.At final follow-up, after a mean of 15.9 years (12 to 20), there was a survivorship of 59% (95% CI 59.6 to 68.9) irrespective of adductor moment group, with a mean time to conversion to knee arthroplasty of 9.5 years (3 to 18; 95% confidence interval ± 2.5).HTO remains a useful option in the medium-term for the treatment of medial compartment osteoarthritis of the knee but does not last in the long-term.Cite this article: Bone Joint J 2016;98-B:601–7.
Long-term results of uncemented total hip arthroplasty with the Taperloc femoral component in patients with Dorr type C proximal femoral morphology
Authors: McLaughlin J. R. , Lee K. R. 
Published: May 2016

Aims To investigate the longevity of uncemented fixation of a femoral component in total hip arthroplasty (THA) in patients with Dorr type C proximal femoral morphology. Patients and Methods A total of 350 consecutive uncemented THA in 320 patients were performed between 1983 and 1987, by a single surgeon using the Taperloc femoral component. The 63 patients (68 hips) with Dorr type C proximal femoral morphology were the focus of this review. The mean age of the patients was 69 years (24 to 88) and mean follow-up was 16.6 years (ten to 29). Survival analysis included eight patients (eight hips) who died without undergoing revision surgery prior to obtaining ten years follow-up. All 55 surviving patients (60 hips) were available for clinical assessment and radiographic review. As a comparator group, the survival and implant fixation in the remaining 282 THAs (257 patients) with Dorr type A and B morphology were evaluated. The mean age of these patients was 52 years (20 to 82). Results In the Dorr C patient group the mean Harris hip score improved from 51 points (21 to 69 points) pre-operatively to 89 (74 to 100) at final follow-up. No femoral component was loose by radiological criteria and osteolysis was only identified around two stems (3.3%). There was one revision (1.6%) of a well-fixed femoral component for sepsis at 11 years. The survival of the Taperloc femoral component at 20 years with revision for any reason as the endpoint was 98% (95% confidence interval; 87 to 99). A total of ten (3.5%) of the Dorr A and B patient group of 282 THAs required revision surgery. Only one (0.4%) for aseptic loosening. A total of two hips (1%) were loose by radiographic criteria and osteolysis occurred around 12 hips (4%). Conclusion This study demonstrates that excellent fixation can be achieved using the Taperloc stem in patients with Dorr type A and B, and Dorr type C bone. Take home message: The Taperloc stem demonstrated equivalent results in Dorr type A and B and Dorr type C bone. Cite this article: Bone Joint J 2016;98-B:595–600.
Revision surgery for the stiff total knee arthroplasty
Authors: Donaldson J. R. , Tudor F. , Gollish J. 
Published: May 2016

AimsThe aim of this study was to examine the results of revision total knee arthroplasty (TKA) undertaken for stiffness in the absence of sepsis or loosening.Patients and MethodsWe present the results of revision surgery for stiff TKA in 48 cases (35 (72.9%) women and 13 (27.1%) men). The mean age at revision surgery was 65.5 years (42 to 83). All surgeries were performed by a single surgeon. Stiffness was defined as an arc of flexion of < 70° or a flexion contracture of > 15°. The changes in the range of movement (ROM) and the Western Ontario and McMasters Osteoarthritis index scores (WOMAC) were recorded.ResultsAt a mean follow up of 59.9 months (12 to 272) there was a mean improvement in arc of movement of 45.0°. Mean flexion improved from 54.4° (5° to 100°) to 90° (10° to 125°) (p < 0.05) and the mean flexion contracture decreased from 12.0° (0° to 45°) to 3.5° (0° to 25°) (p < 0.05). The mean WOMAC scores improved for pain, stiffness and function. In patients with extreme stiffness we describe a novel technique, which we have called the ‘sloppy’ revision. This entails downsizing the polyethylene insert by 4 mm and using a more constrained liner to retain stability.ConclusionTo our knowledge, this is the largest series of revision surgeries for stiffness reported in the literature where infection and loosening have been excluded. Take home message: Whilst revision surgery is technically demanding, improvements in ROM and outcome can be achieved, particularly when the revision is within two years of the primary surgery. Cite this article: Bone Joint J 2016;98-B:622–7.
Graft salvage following infected anterior cruciate ligament reconstruction
Authors: Kuršumović K. , Charalambous C. P. 
Published: May 2016

AimsTo examine the rates of hamstring graft salvage with arthroscopic debridement of infected anterior cruciate ligament (ACL) reconstruction as reported in the literature and discuss functional outcomes.Materials and MethodsA search was performed without language restriction on PubMed, EMBASE, Ovid, CINAHL and Cochrane Register of Controlled Trials (CENTRAL) databases from their inception to April 2015. We identified 147 infected hamstring grafts across 16 included studies. Meta-analysis was performed using a random-effects model to estimate the overall graft salvage rate, incorporating two different definitions of graft salvage.ResultsThe graft salvage rate was 86% (95% confidence intervals (CI) 73% to 93%; heterogeneity: tau2= 1.047, I2= 40.51%, Q = 25.2, df = 15, p < 0.001), excluding ACL re-ruptures. Including re-ruptures as failures, the graft salvage rate was 85% (95% CI 76% to 91%; heterogeneity: tau2 = 0.099, I2= 8.15%, Q = 14.15, df = 13, p = 0.36).ConclusionsArthroscopic debridement combined with antibiotic treatment can lead to successful eradication of infection and graft salvage, with satisfactory functional outcomes in many cases of septic arthritis following ACL reconstruction. Persistent infection despite repeat arthroscopic debridements requires graft removal with the intention of revision ACL surgery at a later stage. Take home message: Arthroscopic debridement combined with antibiotic therapy is an appropriate initial approach in most cases of septic arthritis following ACL reconstruction, achieving graft salvage rates of about 85%. Cite this article: Bone Joint J 2016;98-B:608–15.
The lognormal age of onset distribution in Perthes’ disease
Authors: Perry D. C. , Skellorn P. J. , Bruce C. E. 
Published: May 2016

Aims To explore the of age of onset distribution for Perthes’ disease of the hip, with particular reference to gender, laterality and conformity to the lognormal distribution. Patients and Methods A total of 1082 patients were identified from the Liverpool Perthes’ Disease Register between 1976 and 2010, of which 992 had the date of diagnosis recorded. In total, 682 patients came from the geographical area exclusively served by Alder Hey Hospital, of which 673 had a date of diagnosis. Age of onset curves were analysed, with respect to the predefined subgroups. Results The age of onset demonstrated a positive skew with a median of 5.8 years (interquartile range 4.6 to 7.5). Disease onset was a mean five months earlier in girls (p = 0.01) and one year earlier in those who went on to develop bilateral disease (p < 0.001). There was no difference in the age of onset between geographical districts with differing incidence rates. The entire dataset (n = 992) conformed to a lognormal distribution graphically and with the chi-squared test of normality (p = 0.10), but not using the Shapiro-Wilk test (p = 0.01). The distribution for the predefined geographical subgroup (n = 673) conformed well to a lognormal distribution (chi-squared p = 0.16, Shapiro-Wilk p = 0.08). Given the observed lognormal distribution it was assumed that Perthes’ disease followed on incubation period consistent with a point-source disease exposure. The incubation period was further examined using Hirayama’s method, which suggested that the disease exposure may act in the prenatal period. Conclusion The age of onset in Perthes’ disease conforms to a lognormal distribution, which allows comparisons with infectious disease epidemiology. Earlier onset in girls and those who develop bilateral disease may offer clues to understanding the aetiological determinants of the disease. The analysis suggests that an antenatal aetiological determinant may be responsible for disease. Take home message: Perthes’ disease age of onset conforms to a lognormal model, which is most typical of infectious diseases. The shape of the distribution suggests that an aetiological trigger in the pre-natal period may be an important determinant of disease. Cite this article: Bone Joint J 2016;98-B:710–14.
Asymmetrical ossification in the epiphyseal ring of patients with adolescent idiopathic scoliosis
Authors: Makino T. , Kaito T. , Sakai Y. , Kashii M. , Yoshikawa H. 
Published: May 2016

Aims To clarify the asymmetrical ossification of the epiphyseal ring between the convex and concave sides in patients with adolescent idiopathic scoliosis (AIS). Patients and Methods A total of 29 female patients (mean age, 14.4 years; 11 to 18) who underwent corrective surgery for AIS (Lenke type 1 or 2) were included in our study. In all, 349 vertebrae including 68 apical vertebrae and 87 end vertebrae in the main thoracic (MT) curve and thoracolumbar/lumbar (TL/L) curve were analysed. Coronal sections (anterior, middle and posterior) of the vertebral bodies were reconstructed from pre-operative CT scans (320-row detector; slice thickness, 0.5 mm) and the appearances of the ossification centre in the epiphyseal ring at four corners were evaluated in three groups; all vertebrae excluding end vertebrae, apical vertebrae and end vertebrae. The appearance rates of the ossification centre at the concave and convex sides were calculated and compared. Results The appearance rates of the ossification centres in all vertebrae excluding end vertebrae and apical vertebrae were significantly lower on the concave side than on the convex side in both MT and TL/L curves irrespective of curve flexibility. There was no significant difference in the rate of appearance of the ossification centres on the concave or convex sides in end vertebrae. Conclusion The asymmetric bony growth of vertebral body came into existence at both structural and non-structural curves, and was more apparent around the apical vertebrae. Evaluation of the ossification centre in the epiphyseal ring could be a measure of the effectiveness of brace treatment. Take home message: The ossification of the epiphyseal ring in patients with AIS was delayed or absent on the concave side particularly around the apical vertebrae. Cite this article: Bone Joint J 2016;98-B:666–71.
Short and medium-term outcomes for general surgery in nonagenarian patients in a district general hospital
Authors: Hayes AJ , Davda A , El-Hadi M , Murphy P , Papettas T 
Published: May 2016

Introduction Surgeons are increasingly performing surgery on older patients. There are currently no tools specifically for risk prediction in this group. The aim of this study was to review general surgical operations carried out on patients aged over 90 years and their outcome, before comparing these with predictors of morbidity and mortality. Methods A retrospective review was carried out at our district general hospital of all general surgery patients aged over 90 years who underwent a general surgical operation over a period of 14 years. Information collected included demographics, details of procedures, P-POSSUM (Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity), complications and outcomes. Results A total of 119 procedures were carried out, 72 involving entry into the peritoneal cavity. Overall, 14 patients (12%) died within 30 days and 34 (29%) died within one year. Postoperative complications included infection (56%), renal failure (24%), need for transfusion (17%) and readmission within 30 days (11%). Logistical regression analysis showed that the P-POSSUM correlated well with observed mortality and infection was a significant predictor of in-hospital mortality (p=0.003). Conclusions The P-POSSUM correlates significantly with outcome and should be used when planning major elective or emergency surgery in patients over 90 years of age. Infective complications appear to be a significant predictor of postoperative mortality. This study supports operative intervention as an option in this extreme age group but we emphasise the importance of appropriate patient selection and judicious clinical care.
Determinants of return to work 12 months after total hip and knee arthroplasty
Authors: Leichtenberg CS , Tilbury C , Kuijer PPFM , Verdegaal SHM , Wolterbeek R , Nelissen RGHH , Frings-Dresen MHW , Vliet Vlieland TPM 
Published: May 2016

Introduction A substantial number of patients undergoing total hip or knee arthroplasty (THA or TKA) do not or only partially return to work. This study aimed to identify differences in determinants of return to work in THA and TKA. Methods We conducted a prospective, observational study of working patients aged <65 years undergoing THA or TKA for osteoarthritis. The primary outcome was full versus partial or no return to work 12 months postoperatively. Factors analysed included preoperative sociodemographic and work characteristics, alongside the Hip Disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS), and Oxford Hip and Knee Scores. Results Of 67 THA and 56 TKA patients, 9 (13%) and 10 (19%), respectively, returned partially and 5 (7%) and 6 (11%), respectively, did not return to work 1 year postoperatively. Preoperative factors associated with partial or no return to work in THA patients were self-employment, absence from work and a better HOOS Activities of Daily Living (ADL) subscale score, whereas only work absence was relevant in TKA patients. Type of surgery modified the impact of ADL scores on return to work. Conclusions In both THA and TKA, absence from work affected return to work, whereas self-employment and better preoperative ADL subscale scores were also associated in THA patients. The impact of ADL scores on return to work was modified by type of surgery. These results suggest that strategies aiming to influence modifiable factors should consider THA and TKA separately.
Book Reviews
Authors: Kaiser Susan B. , Chenoune Farid , Franklin Kathryn 
Published: May 2016

Abstract
Cultural Passions: Fans, Aesthetes, and Tarot Readers, Elizabeth Wilson (2013, first edition) London: I.B. Tauris, 240 pp., ISBN: 978-1780762869, Hardback, $90.00; Paperback, $28.00
Credit, Fashion, Sex: Economies of Regard in Old Regime France, Clare Haru Crowston (2013, first edition) Durham and London: Duke University Press, 424 pp., ISBN 978-0-8223-5528-1, Paperback, $27.95
Aesthetic Politics in Fashion, Elke Gaugele (ed.) (2014, first edition) Berlin: Sternberg Press, 260 pp., ISBN 9783956790799, Paperback, €22.00