Generalised Apery numbers modulo 9

Whilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC

Short term ex-vivo expansion of circulating head and neck tumour cells.

Minimally invasive techniques are required for the identification of head and neck cancer (HNC) patients who are at an increased risk of metastasis, or are not responding to therapy. An approach utilised in other solid cancers is the identification and enumeration of circulating tumour cells (CTCs) in the peripheral blood of patients. Low numbers of CTCs has been a limiting factor in the HNC field to date. Here we present a methodology to expand HNC patient derived CTCs ex-vivo. As a proof of principle study, 25 advanced stage HNC patient bloods were enriched for circulating tumour cells through negative selection and cultured in 2D and 3D culture environments under hypoxic conditions (2% O2, 5% CO2). CTCs were detected in 14/25 (56%) of patients (ranging from 1-15 CTCs/5 mL blood). Short term CTC cultures were successfully generated in 7/25 advanced stage HNC patients (5/7 of these cultures were from HPV+ patients). Blood samples from which CTC culture was successful had higher CTC counts (p = 0.0002), and were predominantly from HPV+ patients (p = 0.007). This is, to our knowledge, the first pilot study to culture HNC CTCs ex-vivo. Further studies are warranted to determine the use of short term expansion in HNC and the role of HPV in promoting culture success

A Brownian particle in a microscopic periodic potential

We study a model for a massive test particle in a microscopic periodic potential and interacting with a reservoir of light particles. In the regime considered, the fluctuations in the test particle's momentum resulting from collisions typically outweigh the shifts in momentum generated by the periodic force, and so the force is effectively a perturbative contribution. The mathematical starting point is an idealized reduced dynamics for the test particle given by a linear Boltzmann equation. In the limit that the mass ratio of a single reservoir particle to the test particle tends to zero, we show that there is convergence to the Ornstein-Uhlenbeck process under the standard normalizations for the test particle variables. Our analysis is primarily directed towards bounding the perturbative effect of the periodic potential on the particle's momentum.Comment: 60 pages. We reorganized the article and made a few simplifications of the conten

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Variation in guideline implementation and adherence regarding severe traumatic brain injury treatment: a CENTER-TBI survey study in Europe

Guidelines may reduce practice variation and optimize patient care. We aimed to study differences in guideline use in the management of traumatic brain injury (TBI) patients and analyze reasons for guideline non-adherence. As part of a prospective, observational, multi-center European cohort study, participants from 68 centers in 20 countries were asked to complete 72-item questionnaires regarding their management of severe TBI. Six questions with multiple sub-questions focused on guideline use and implementation. Questionnaires were completed by 65 centers. Of these, 49 (75%) reported use of the Brain Trauma Foundation Guidelines for the medical management of TBI or related institutional protocols, 11 (17%) used no guidelines and 5 used other guidelines (8%). Of 54 centers reporting use of any guidelines, 41 (75%) relied on written guidelines. Four centers of the 54 (7%) reported no formal implementation efforts. Structural attention to the guidelines during daily clinical rounds was reported by 21 centers (38%). The most often reported reasons for non-adherence were ‘every patient is unique’ and the presence of extracranial injuries, both for centers that did and did not report the use of guidelines. There is substantial variability in the use and implementation of guidelines in neurotrauma centers in Europe. Further research is needed to strengthen the evidence underlying guidelines and to overcome implementation barriers

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer

Kallikrein-related peptidase 14 (KLK14) is one of several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumour microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analysed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic and in vitro assays with the goal to identify substrates, related-signalling pathways and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neo-adjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression re-occurred in patients who developed castrate-resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14-substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14-regulated genes (Interleukin 32, midkine, Sox9), particularly an involvement of the MAPK1 and IL1RN pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumours. Additional work is necessary to determine the benefits and implications of targeting/co-targeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel �10,000 solar masses of material at velocities exceeding 1,000 km/s. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of the thermonuclear runaway, prolonged optically thick winds, or binary interaction with the nova envelope. Classical novae are now routinely detected in GeV gamma-rays, suggesting that relativistic particles are accelerated by strong shocks in nova ejecta. Here we present high-resolution imaging of the gamma-ray-emitting nova V959 Mon at radio wavelengths, showing that its ejecta were shaped by binary motion: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are gamma-ray emitters

Condensate cosmology in O'Raifeartaigh models

Flat directions charged under an R-symmetry are a generic feature of O'Raifeartaigh models. Non-topological solitons associated with this symmetry, R-balls, are likely to form through the fragmentation of a condensate, itself created by soft terms induced during inflation. In gravity mediated SUSY breaking R-balls decay to gravitinos, reheating the universe. For gauge mediation R-balls can provide a good dark matter candidate. Alternatively they can decay, either reheating or cooling the universe. Conserved R-symmetry permits decay to gravitinos or gauginos, whereas spontaneously broken R-symmetry results in decay to visible sector gauge bosons.Comment: 29 pages, 5 figures. Comments and references added, accepted for publication in JHE