Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

BackgroundAt the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment.MethodsWe conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m2, overweight 25-29.9 kg/m2 and obese ⩾30 kg/m2). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk.ResultsOn crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant.ConclusionsOverweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM

Analysis of the Brinkman-Forchheimer equations with slip boundary conditions

In this work, we study the Brinkman-Forchheimer equations driven under slip boundary conditions of friction type. We prove the existence and uniqueness of weak solutions by means of regularization combined with the Faedo-Galerkin approach. Next we discuss the continuity of the solution with respect to Brinkman's and Forchheimer's coefficients. Finally, we show that the weak solution of the corresponding stationary problem is stable

Evaluation of a community pharmacy-led test-and-treat service for women with uncomplicated lower urinary tract infection in England

Background Uncomplicated lower urinary tract infections (UTIs) are common in women consulting primary healthcare, taking up GP resources. Delayed consultation can increase the risk of serious infections such as pyelonephritis or bacteraemia. Objectives To evaluate the effectiveness and uptake of a lower UTI test-and-treat service for women presenting with urinary symptoms within a community pharmacy in supporting self-care and appropriate use of antibiotics and reducing demand on other NHS resources. Methods The service was aligned to national guidelines to diagnose and treat lower UTI in women aged 16–64 years and used national resources to provide safety-netting and self-care advice. Consultation included clinical assessment and a urine dipstick test alongside a novel smartphone app, with diagnosis informed by test results. Women were provided with safety-netting advice and either advised on self-care, supplied with antibiotics or referred to their GP. Results Data were analysed for 764 women who presented to 23 pharmacies during December 2018 to April 2019. Lower UTI was found to be likely in 372/496 (75.0%) women, most of whom purchased antibiotics on the same day. Had the service not been available, approximately three-quarters of women who had completed the service and responded to the question would have visited their GP (214/301) and more than one-third would have used self-care with or without going to see their GP (116/301). Conclusions A community pharmacy-led UTI test-and-treat service for women aged 16–64 years presenting with urinary symptoms provided accessible and timely care aligned to national guidance, with 75.0% of consultations requiring antibiotic treatment

Sequence Skill Acquisition and Off-Line Learning in Normal Aging

It is well known that certain cognitive abilities decline with age. The ability to form certain new declarative memories, particularly memories for facts and events, has been widely shown to decline with advancing age. In contrast, the effects of aging on the ability to form new procedural memories such as skills are less well known, though it appears that older adults are able to acquire some new procedural skills over practice. The current study examines the effects of normal aging on procedural memory more closely by comparing the effects of aging on the encoding or acquisition stage of procedural learning versus its effects on the consolidation, or between-session stage of procedural learning. Twelve older and 14 young participants completed a sequence-learning task (the Serial Reaction Time Task) over a practice session and at a re-test session 24 hours later. Older participants actually demonstrated more sequence skill during acquisition than the young. However, older participants failed to show skill improvement at re-test as the young participants did. Age thus appears to have a differential effect upon procedural learning stages such that older adults' skill acquisition remains relatively intact, in some cases even superior, compared to that of young adults, while their skill consolidation may be poorer than that of young adults. Although the effect of normal aging on procedural consolidation remains unclear, aging may actually enhance skill acquisition on some procedural tasks

Steps in the bacterial flagellar motor

The bacterial flagellar motor is a highly efficient rotary machine used by many bacteria to propel themselves. It has recently been shown that at low speeds its rotation proceeds in steps [Sowa et al. (2005) Nature 437, 916--919]. Here we propose a simple physical model that accounts for this stepping behavior as a random walk in a tilted corrugated potential that combines torque and contact forces. We argue that the absolute angular position of the rotor is crucial for understanding step properties, and show this hypothesis to be consistent with the available data, in particular the observation that backward steps are smaller on average than forward steps. Our model also predicts a sublinear torque-speed relationship at low torque, and a peak in rotor diffusion as a function of torque

Preliminary report of a gas conditioner to improve operational reliability of cryotherapy in developing countries

BACKGROUND: Cryotherapy is a safe, affordable, and effective method of treatment for cervical intraepithelial neoplasia. In some low-resource settings, environmental conditions or qualities of the refrigerant gas can lead to blockage of cryotherapy equipment, terminating treatment. A prototype of a gas conditioner to prevent operational failure was designed, built, and field tested. METHODS: The prototype conditioner device consists of an expansion chamber that filters and dries the refrigerant gas. Users in Peru and Kenya reported on their experience with the prototype conditioner. In Ghana, simulated cryotherapy procedures were used to test the effects of the prototype conditioner, as well as the commonly used "cough technique." RESULTS: Anecdotal reports from field use of the device were favorable. During simulated cryotherapy, the prevalence of blockage during freezing were 0% (0/25) with the device alone, 23.3% (7/30) with the cough technique alone, 5.9% (1/17) with both, and 55.2% (16/29) with neither (Pearson's Chi square = 26.6, df = 3, p < 0.001 (comparison amongst all groups)). CONCLUSION: This prototype design of a cryotherapy gas conditioner is a potential solution for low-resource settings that are experiencing cryotherapy device malfunction

Spatially valid proprioceptive cues improve the detection of a visual stimulus

Vision and proprioception are the main sensory modalities that convey hand location and direction of movement. Fusion of these sensory signals into a single robust percept is now well documented. However, it is not known whether these modalities also interact in the spatial allocation of attention, which has been demonstrated for other modality pairings. The aim of this study was to test whether proprioceptive signals can spatially cue a visual target to improve its detection. Participants were instructed to use a planar manipulandum in a forward reaching action and determine during this movement whether a near-threshold visual target appeared at either of two lateral positions. The target presentation was followed by a masking stimulus, which made its possible location unambiguous, but not its presence. Proprioceptive cues were given by applying a brief lateral force to the participant’s arm, either in the same direction (validly cued) or in the opposite direction (invalidly cued) to the on-screen location of the mask. The d′ detection rate of the target increased when the direction of proprioceptive stimulus was compatible with the location of the visual target compared to when it was incompatible. These results suggest that proprioception influences the allocation of attention in visual spac

Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations

Background: Pulmonary arteriovenous malformations (PAVMs) generate a right-to-left shunt. Impaired gas exchange results in hypoxemia and impaired CO2 clearance. Most patients compensate effectively but a proportion are dyspneic, and these are rarely the most hypoxaemic. Aim: To test degrees of concurrent pathology influencing exercise capacity. Design: Replicate, sequential single centre, prospective studies. Methods: Cardiopulmonary exercise tests (CPET) were performed in 26 patients with PAVMs, including individuals with and without known airflow obstruction. To replicate, relationships were tested prospectively in an independent cohort where self-reported exercise capacity evaluated by the Veterans Specific Activity Questionnaire (VSAQ) was used to calculate metabolic equivalents at peak exercise (METS N = 71). Additional measurements included oxygen saturation (SpO2), forced expiratory volume in 1 second (FEV1), vital capacity (VC), exhaled nitric oxide (FeNO), haemoglobin and iron indices. Results: By CPET, the peak work-rate was only minimally associated with low SpO2 or low arterial oxygen content (CaO2=1.34 x SpO2 x haemoglobin), but was reduced in patients with low FEV1 or VC. Supranormal work-rates were seen in patients with severe right-to-left shunting and SpO2 80% predicted. VSAQ-calculated METS also demonstrated little relationship with SpO2, and in crude and CaO2-adjusted regression, were lower in patients with lower FEV1 or VC. Bronchodilation increased airflow even where spirometry was in the normal range: exhaled nitric oxide measurements were normal in 80% of cases, and unrelated to any PAVM-specific variable. Conclusions: Exercise capacity is reduced by relatively mild airflow limitation (obstructive or restrictive) in the setting of PAVMs

Lead Levels and Ischemic Heart Disease in a Prospective Study of Middle-Aged and Elderly Men: the VA Normative Aging Study

Background: Lead exposure has been associated with higher blood pressure, hypertension, electrocardiogram abnormalities, and increased mortality from circulatory causes.Objective We assessed the association between bone lead—a more accurate biomarker of chronic lead exposure than blood lead—and risk for future ischemic heart disease (IHD). Methods: In a prospective cohort study (VA Normative Aging Study), 837 men who underwent blood or bone lead measurements at baseline were followed-up for an ischemic heart disease event between 1 September 1991 and 31 December 2001. IHD was defined as either a diagnosis of myocardial infarction or angina pectoris that was confirmed by a cardiologist. Events of fatal myocardial infarction were assessed from death certificates. Results: An IHD event occurred in 83 cases (70 nonfatal and 13 fatal). The mean blood, tibia, and patella lead levels were higher in IHD cases than in noncases. In multivariate Cox-proportional hazards models, one standard deviation increase in blood lead level was associated with a 1.27 (95% confidence interval, 1.01–1.59) fold greater risk for ischemic heart disease. Similarly, a one standard deviation increase in patella and tibia lead levels was associated with greater risk for IHD (hazard ratio for patella lead = 1.29; 95% confidence interval, 1.02–1.62). Conclusions: Men with increased blood and bone lead levels were at increased risk for future IHD. Although the pathogenesis of IHD is multifactorial, lead exposure may be one of the risk factors