bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and associated harm of engagement in self-asphyxial behaviours (‘choking game’) in young people: a systematic review
Authors: Busse H , Harrop T , Gunnell D , Kipping R 
Published: June 2015

ObjectiveTo assess the prevalence of engagement in self-asphyxial (risk-taking) behaviour (SAB) (‘choking game’) and associated morbidity and mortality in children and young people up to age 20.DesignSystematic literature review.Search strategyElectronic database search of MEDLINE, Embase, PsycINFO, CINAHL, PubMed, Web of Science Core Collection, BIOSIS citation index and the Cochrane register with no language or date limits applied. References of key papers were reviewed, and experts were contacted to identify additional relevant papers.Eligibility criteriaSystematic reviews, cross-sectional, cohort and case–control studies, and case reports examining SAB with regard to individuals aged 0–20 years, without explicitly stated autoerotic, suicidal or self-harm intentions were included.ResultsThirty-six relevant studies were identified, and SAB was reported in 10 countries. In North America, France and Colombia, awareness of SAB ranged from 36% to 91% across studies/settings, and the median lifetime prevalence of engagement in SAB was 7.4%. Six studies identified the potential for SAB to be associated with engagement in other risk behaviours. Ninety-nine fatal cases were reported. Of the 24 cases described in detail, most occurred when individuals engaged in SAB alone and used a ligature.ConclusionsThe current evidence on SAB among young people is limited, and stems predominantly from North America and France. Awareness of SAB among young people is high, and engagement varies by setting. Further research is needed to understand the level of risk and harm associated with SAB, and to determine the appropriate public health response.
Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation
Authors: Sharma Pawana , Scotland Graham , Cruickshank Moira , Tassie Emma , Fraser Cynthia , Burton Christopher , Croal Bernard , Ramsay Craig R , Brazzelli Miriam 
Published: June 2015

ObjectivesTo investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care.DesignSystematic review of current evidence and economic modelling.Data sourcesMajor electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts.Study eligibility criteriaRandomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered.Results26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p≤0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were £7324 with standard care and £7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have ∼80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of £20 000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not.ConclusionsSelf-monitoring appears to be a safe and cost-effective option.Trial registration numberPROSPERO CRD42013004944.
SSRI use and risk of fractures among perimenopausal women without mental disorders
Authors: Sheu Yi-han , Lanteigne Amy , Stürmer Til , Pate Virginia , Azrael Deborah , Miller Matthew 
Published: June 2015

BackgroundSelective serotonin reuptake inhibitors (SSRIs) were recently approved by the FDA to treat vasomotor symptoms associated with menopause. No prior study has directly examined whether fracture risk is increased among perimenopausal women who initiate SSRIs or among a population of women without mental disorders more generally.MethodsFemale patients without mental illness, aged 40–64 years, who initiated SSRIs were compared with a cohort who initiated H2 antagonists (H2As) or proton-pump inhibitors (PPIs) in 1998–2010, using data from a claims database. Standardised mortality ratio weighting was applied using the propensity score odds of treatment to adapt the distribution of characteristics among patients starting H2A/PPIs to the distribution among SSRI initiators. Poisson regression estimated risk differences and Cox proportional hazards regression the RR of fractures among new users of SSRIs versus H2A/PPIs. Primary analyses allowed for a 6-month lag period (ie, exposure begins 6 months after initiation) to account for a hypothesised delay in the onset of any clinically meaningful effect of SSRIs on bone mineral density.ResultsFracture rates were higher among the 137 031 SSRI initiators compared with the 236 294 H2A/PPI initiators, with HRs (SSRI vs H2A/PPI) over 1, 2 and 5 years of 1.76 (95% CI 1.33 to 2.32), 1.73 (95% CI 1.33 to 2.24) and 1.67 (95% CI 1.30 to 2.14), respectively.ConclusionsSSRIs appear to increase fracture risk among middle-aged women without psychiatric disorders, an effect sustained over time, suggesting that shorter duration of treatment may decrease fracture risk. Future efforts should examine whether this association pertains at lower doses.
The influence of chronic health problems and work-related factors on loss of paid employment among older workers
Authors: Leijten Fenna R M , de Wind Astrid , van den Heuvel Swenne G , Ybema Jan Fekke , van der Beek Allard J , Robroek Suzan J W , Burdorf Alex 
Published: June 2015

BackgroundWith an ageing society and increasing retirement ages, it is important to understand how employability can be promoted in older workers with health problems. The current study aimed to determine whether (1) different chronic health problems predict transitions from paid employment to disability benefits, unemployment and early retirement, and (2) how work-related factors modify these associations.MethodsSelf-report questionnaire data was used from the Dutch longitudinal Study on Transitions in Employment, Ability and Motivation with 3 years of follow-up (2010–2013), among employees aged 45–64 years (N=8149). The influence of baseline chronic health problems and work-related factors on transitions from paid employment to disability benefits, unemployment and early retirement during follow-up was estimated in a competing risks proportional hazards model. Relative excess risk of transitions due to the interaction between chronic health problems and work-related factors was assessed.ResultsSevere headache, diabetes mellitus and musculoskeletal, respiratory, digestive and psychological health problems predicted an increased risk of disability benefits (HR range 1.78–2.79). Circulatory (HR=1.35) and psychological health problems (HR=2.58) predicted unemployment, and musculoskeletal (HR=1.23) and psychological health problems (HR=1.57) predicted early retirement. Work-related factors did not modify the influence of health problems on unemployment or early retirement. Psychosocial work-related factors, especially autonomy, modified the influence of health problems on disability benefits. Specifically, among workers with health problems, higher autonomy, higher support and lower psychological job demands reduced the risk of disability benefits by 82%, 49%, and 11%, respectively.ConclusionsAll health problems affected disability benefits to a similar extent, but psychological health problems especially predicted unemployment and early retirement. For older workers with health problems, promoting an optimal work environment has the potential to contribute to sustainable employment.
Endovascular treatment of unruptured ophthalmic artery aneurysms: clinical usefulness of the balloon occlusion test in predicting vision outcomes after coil embolization
Authors: Kim Byungjun , Jeon Pyoung , Kim Keonha , Yang Narae , Kim Sungtae , Kim Hyungjin , Byun Hongsik , Jo Kyung-Il 
Published: June 2015

BackgroundEndovascular coil embolization for ophthalmic artery (OphA) aneurysms has the latent risk of occlusion of the OphA during the procedure, which can lead to loss of vision. We report clinical and angiographic results of endovascular treatment of OphA aneurysms together with the efficacy of the balloon occlusion test (BOT).MethodsFrom August 2005 to December 2013, 31 consecutive patients with 33 OphA aneurysms were treated in our institution. The patients were classified into two groups according to the location of the OphA within the aneurysmal sac. The BOT was performed in 28 patients using a hypercompliant balloon before endovascular coiling. Collateral circulation between the external carotid artery and the OphA was examined and visual function tests were performed before and after treatment. Patient demographics, angiographic and clinical outcomes were reviewed.ResultsAmong the 28 patients who underwent the BOT, intact collateral circulation was demonstrated in 26 (92.9%) patients and complete occlusion of the OphA was obtained in three patients after coiling. Retrograde filling of the OphA with choroidoretinal blush was observed on post-procedural angiography and no specific visual symptoms were reported during the follow-up period. Complete embolization was achieved in 30 lesions (96.8%) and only five patients (16.1%) had minor recanalization.ConclusionsEndovascular treatment of OphA aneurysms can be performed safely and effectively in conjunction with BOT. The BOT may give useful information to predict visual outcome in patients whose OphA is likely to be threatened by the coiling procedure and to determine the optimal treatment strategy.
Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure
Authors: Mease P , Deodhar A , Fleischmann R , Wollenhaupt J , Gladman D , Leszczyński P , Vitek P , Turkiewicz A , Khraishi M , FitzGerald O , Landewé R , de Longueville M , Hoepken B , Peterson L , van der Heijde D 
Published: June 2015

ObjectivePrevious reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA.MethodsRAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data.ResultsOf 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events.ConclusionsCZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure.Trial registration numberNCT01087788.
Alfaxalone‐butorphanol‐dexmedetomidine anaesthesia in striped skunks (Mephitis mephitis) undergoing skin biopsy: two cases
Authors: d'Ovidio Dario , Noviello Emilio , Nocerino Maurizio , Adami Chiara 
Published: June 2015

Skunks are becoming increasingly popular as pets. As such, they often undergo a variety of surgical procedures. Two pet skunks undergoing a dermatological examination, including skin biopsy, were anaesthetised with a combination of dexmedetomidine (0.02 mg/kg), butorphanol (0.3 mg/kg), and alfaxalone (4 mg/kg), all administered intramuscularly. Anaesthesia was characterised by rapid onset, absence of detectable side effects and fast recovery after atipamezole administration. Biopsies and toe‐pinch did not elicit cardiorespiratory responses, nor did it result in movements or lightening of the anaesthetic depth. Both skunks recovered uneventfully, and showed normal appetite and regular defecation within eight hours following surgery. However, both the animals experienced mild hypothermia at recovery. The dexmedetomidine‐alfaxalone‐butorphanol combination produced satisfactory anaesthesia in the two skunks, object of this report. This anaesthetic protocol may be used in this species to provide immobility, myorelaxation, unconsciousness and analgesia during skin biopsy or other minor surgical procedures.
Role of rift transection and punctuated subsidence in the development of the North Falkland Basin
Authors: Lohr Tina , Underhill John R. 
Published: June 2015

The results of well-constrained seismic interpretation and new mapping of three-dimensional (3D) seismic data volumes demonstrates that the North Falkland Basin consists of two superimposed failed rift basins: a Late Jurassic NW–SE-striking Southern Rift Basin (SRB); and an Early Cretaceous north–south-striking Northern Rift Basin (NRB).
The SRB is best developed in coastal waters of the Falkland Islands, where it comprises a series of extensional sub-basins that are transected by faults belonging to the more substantive NRB. Regional interpretation demonstrates that the NRB consists of a southward-tapering, asymmetric extensional basin containing a thick (in excess of 10 km) sequence of sediments. Its syn-rift subsidence history was controlled by a major west-dipping normal fault array comprising several fault segment precursors, which, together with corresponding antithetic faults, effectively subdivides the hanging wall into a series of sub-basins throughout its length.
The NRB initially developed in a fluvial and later lacustrine environment before becoming predominantly marine in the Tertiary. A prograding delta system filled the basin from the north during the early post-rift phase. Contemporaneously, sediment was shed off the segmented basin-bounding fault via long-established feeder drainage systems through breached relay ramps into the depocentre. The resultant sediment dispersal led to deposition of numerous lacustrine turbidites that created the Sea Lion fans and its affiliates, the location of which mimics, and is thus interpreted to have been controlled by, the underlying syn-rift sub-basins.
Post-rift subsidence was punctuated by an important, but short-lived, phase of basin inversion during the Aptian that created a large, broad and gentle north–south-striking anticline that runs along the central basin axis. Whilst the episode of basin inversion arrested subsidence, it did not inhibit petroleum prospectivity. The syn-rift lacustrine source intervals did subsequently pass through the critical moment in the Cretaceous leading to hydrocarbon maturation and the migration of waxy oil, a process that continues to the present day.
Higher Body Mass Index Is Associated with Subjective Olfactory Dysfunction
Authors: Patel Z. M. , DelGaudio J. M. , Wise S. K. 
Published: June 2015

Background. Morbidly obese patients demonstrate altered olfactory acuity. There has been no study directly assessing Body Mass Index (BMI) in patients with olfactory dysfunction. Our purpose was to compare BMI in a group of patients with subjective olfactory dysfunction to those without subjective olfactory complaints.Methods. Retrospective matched case-control study. Sixty patients who presented to a tertiary care otolaryngology center with subjective smell dysfunction over one year were identified. Neoplastic and obstructive etiologies were excluded. Demographics, BMI, and smoking status were reviewed. Sixty age, gender, and race matched control patients were selected for comparison. Chi-square testing was used.Results. 48 out of 60 patients (80%) in the olfactory dysfunction group fell into the overweight or obese categories, compared to 36 out of 60 patients (60%) in the control group. There was a statistically significant difference between the olfactory dysfunction and control groups for this stratified BMI(p= 0.0168).  Conclusion. This study suggests high BMI is associated with olfactory dysfunction. Prospective clinical research should examine this further to determine if increasing BMI may be a risk factor in olfactory loss and to elucidate what role olfactory loss may play in diet and feeding habits of obese patients.
Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice
Authors: Sanmamed Miguel F. , Rodriguez Inmaculada , Schalper Kurt A. , Oñate Carmen , Azpilikueta Arantza , Rodriguez-Ruiz Maria E. , Morales-Kastresana Aizea , Labiano Sara , Pérez-Gracia Jose L. , Martín-Algarra Salvador , Alfaro Carlos , Mazzolini Guillermo , Sarno Francesca , Hidalgo Manuel , Korman Alan J. , Jure-Kunkel Maria , Melero Ignacio 
Published: June 2015

AbstractA current pressing need in cancer immunology is the development of preclinical model systems that are immunocompetent for the study of human tumors. Here, we report the development of a humanized murine model that can be used to analyze the pharmacodynamics and antitumor properties of immunostimulatory monoclonal antibodies (mAb) in settings where the receptors targeted by the mAbs are expressed. Human lymphocytes transferred into immunodeficient mice underwent activation and redistribution to murine organs, where they exhibited cell-surface expression of hCD137 and hPD-1. Systemic lymphocyte infiltrations resulted in a lethal CD4+ T cell–mediated disease (xenograft-versus-host disease), which was aggravated when murine subjects were administered clinical-grade anti-hCD137 (urelumab) and anti-hPD-1 (nivolumab). In mice engrafted with human colorectal HT-29 carcinoma cells and allogeneic human peripheral blood mononuclear cells (PBMC), or with a patient-derived gastric carcinoma and PBMCs from the same patient, we found that coadministration of urelumab and nivolumab was sufficient to significantly slow tumor growth. Correlated with this result were increased numbers of activated human T lymphocytes producing IFNγ and decreased numbers of human regulatory T lymphocytes in the tumor xenografts, possibly explaining the efficacy of the therapeutic regimen. Our results offer a proof of concept for the use of humanized mouse models for surrogate efficacy and histology investigations of immune checkpoint drugs and their combinations. Cancer Res; 75(17); 3466–78. ©2015 AACR.
Therapeutic Targeting of the Warburg Effect in Pancreatic Cancer Relies on an Absence of p53 Function
Authors: Rajeshkumar N.V. , Dutta Prasanta , Yabuuchi Shinichi , de Wilde Roeland F. , Martinez Gary V. , Le Anne , Kamphorst Jurre J. , Rabinowitz Joshua D. , Jain Sanjay K. , Hidalgo Manuel , Dang Chi V. , Gillies Robert J. , Maitra Anirban 
Published: June 2015

Abstract
The “Warburg effect” describes a peculiar metabolic feature of many solid tumors, namely their increased glucose uptake and high glycolytic rates, which allow cancer cells to accumulate building blocks for the biosynthesis of macromolecules. During aerobic glycolysis, pyruvate is preferentially metabolized to lactate by the enzyme lactate dehydrogenase-A (LDH-A), suggesting a possible vulnerability at this target for small-molecule inhibition in cancer cells. In this study, we used FX11, a small-molecule inhibitor of LDH-A, to investigate this possible vulnerability in a panel of 15 patient-derived mouse xenograft (PDX) models of pancreatic cancer. Unexpectedly, the p53 status of the PDX tumor determined the response to FX11. Tumors harboring wild-type (WT) TP53 were resistant to FX11. In contrast, tumors harboring mutant TP53 exhibited increased apoptosis, reduced proliferation indices, and attenuated tumor growth when exposed to FX11. [18F]-FDG PET-CT scans revealed a relative increase in glucose uptake in mutant TP53 versus WT TP53 tumors, with FX11 administration downregulating metabolic activity only in mutant TP53 tumors. Through a noninvasive quantitative assessment of lactate production, as determined by 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate, we confirmed that FX11 administration inhibited pyruvate-to-lactate conversion only in mutant TP53 tumors, a feature associated with reduced expression of the TP53 target gene TIGAR, which is known to regulate glycolysis. Taken together, our findings highlight p53 status in pancreatic cancer as a biomarker to predict sensitivity to LDH-A inhibition, with regard to both real-time noninvasive imaging by 13C MRS as well as therapeutic response. Cancer Res; 75(16); 3355–64. ©2015 AACR.
Neutrophils Increase Oral Squamous Cell Carcinoma Invasion through an Invadopodia-Dependent Pathway
Authors: Glogauer Judah E. , Sun Chun X. , Bradley Grace , Magalhaes Marco A.O. 
Published: June 2015

AbstractNeutrophils have recently been shown to promote invasion and correlate with a poor prognosis in different cancers, including head and neck squamous cell carcinomas. In this study, we analyze the effects of neutrophils in the invasion of oral squamous cell carcinoma (OSCC) using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and UMSCC47 cells (OSCC cell line). Invasion and matrix degradation were determined using a modified in vitro invasion assay and an invadopodia assay, respectively. UMSCC47 and neutrophil cocultures or conditioned media from cocultures increased UMSCC47 invasion, invadopodia formation, and matrix degradation. Further analysis revealed an increase in TNFα and IL8 in supernatants of cocultures compared with neutrophil or UMSCC47 cultures alone and that inhibition of TNFα and IL8 significantly decreased OSCC invasion. Our results show that neutrophils increase the invasiveness of OSCC through the activation of invadopodia and matrix degradation, suggesting a paracrine activation loop between the two cells. Importantly, the presence of neutrophils in the oral environment may modulate the clinical behavior of OSCC. Cancer Immunol Res; 3(11); 1218–26. ©2015 AACR.