The HEV Ventilator: at the interface between particle physics and biomedical engineering.

A high-quality, low-cost ventilator, dubbed HEV, has been developed by the particle physics community working together with biomedical engineers and physicians around the world. The HEV design is suitable for use both in and out of hospital intensive care units, provides a variety of modes and is capable of supporting spontaneous breathing and supplying oxygen-enriched air. An external air supply can be combined with the unit for use in situations where compressed air is not readily available. HEV supports remote training and post market surveillance via a Web interface and data logging to complement standard touch screen operation, making it suitable for a wide range of geographical deployment. The HEV design places emphasis on the ventilation performance, especially the quality and accuracy of the pressure curves, reactivity of the trigger, measurement of delivered volume and control of oxygen mixing, delivering a global performance which will be applicable to ventilator needs beyond the COVID-19 pandemic. This article describes the conceptual design and presents the prototype units together with a performance evaluation.

Olanzapine-induced acute necrotising pancreatitis leading to recurrent multiple organ dysfunction syndrome.

A married mother in her 50s acutely developed vomiting, diarrhoea and severe epigastric pain 2 weeks following discharge from an acute psychiatric inpatient unit. She presented to the emergency department complaining of a 2-day history of the above symptoms. Blood tests revealed neutrophilia, grossly raised inflammatory markers and amylase levels triple the normal range. Based on radiological investigations, she was treated for necrotising pancreatitis that quickly escalated to multi-system organ failure and a lengthy intensive care unit admission. Common causes of pancreatitis, including cholelithiasis, alcohol and other drugs, were ruled out. Despite this, she suffered recurrent episodes of pancreatitis with significant morbidity. Olanzapine, started during her psychiatric admission, was determined to be the offending agent. Two years following the discontinuation of olanzapine, the patient has had no further episodes of acute pancreatitis.

School Nursing Protocol for the Management of Human Bites.

Human biting is considered a common stage in pediatric infant growth and development. However, this stage is not considered appropriate once children enter group daycare and school settings, and such behavior can lead to injury, stress, and trauma for other students and staff. When biting occurs in the school setting, staff are often unprepared to respond appropriately, and may seek delayed care, if at all. The school nurse may also be ill-equipped to provide first aid and education if there are no standardized guidelines to follow. Having a protocol in place for human bite incidents in the school setting helps school nurses provide information to students, parents, and staff in a timely manner and assists them with following evidence-based practice. Accurate documentation of the incidents also allows school nurses to identify triggers and knowledge deficits, which can assist them in planning educational interventions and training in the school setting.

Mid-term outcomes of a male retro-urethral, transobturator synthetic sling for treatment of post-prostatectomy incontinence: Impact of radiotherapy and storage dysfunction.

PURPOSE: To determine mid-term durability of the AdVance sling for post-prostatectomy incontinence (PPI) and impact of prior radiotherapy and storage dysfunction. METHOD: Eighty men undergoing AdVance sling for PPI during 2008-2013 were reviewed. Pre-op urodynamics, pre and post-op pad usage, prior radiotherapy, and PGI-I scores were recorded. RESULT: Mean follow-up was 36 months (range 14-72). Twelve men had radiotherapy pre-op, 10 had detrusor overactivity (DO), and 20 reduced compliance. Pre-op mean 24-hr pad weight was 264 g and mean pads-per-day (PPD) 2.60 ± 0.29. In the early post-op period (3-6 months), mean PPD was 0.40 (SD 0.16); at mid-term follow-up mean PPD was 1.02 ± 0.31. Radiotherapy and DO were independently predictive of poor mid-term outcome. Men with DO or radiotherapy were using 1.03 ± 0.42 (P = 0.019) and 1.17 ± 0.41 (P = 0.02) more PPD, respectively than men without these factors. At mid-term follow-up, men without radiotherapy or DO were using 1.98 ± 0.28 less PPD compared to pre-operatively (P < 0.0001); with radiotherapy or DO men were using 0.73 ± 0.38 (P = 0.057) and 0.72 ± 0.43 (P = 0.092) less PPD, respectively. PGI-I score for men without radiotherapy or DO was 1.98 ± 0.40 ("much better"); with radiotherapy or DO PGI-I score was 3.80 ± 0.49 ("no difference"). CONCLUSION: The AdVance sling provides mid-term improvement in men with PPI. However, men with radiotherapy or DO have significantly poorer outcomes with mid-term results indicating a return to baseline degree of incontinence. Caution should be taken when considering the AdVance sling in these men. Pre-op urodynamics in men with radiotherapy and/or overactive bladder may be important when considering men for AdVance sling. Neurourol. Urodynam. 36:1147-1150, 2017. © 2016 Wiley Periodicals, Inc.

Cell cycle-dependent phosphorylation of Sec4p controls membrane deposition during cytokinesis.

Intracellular trafficking is an essential and conserved eukaryotic process. Rab GTPases are a family of proteins that regulate and provide specificity for discrete membrane trafficking steps by harnessing a nucleotide-bound cycle. Global proteomic screens have revealed many Rab GTPases as phosphoproteins, but the effects of this modification are not well understood. Using the Saccharomyces cerevisiae Rab GTPase Sec4p as a model, we have found that phosphorylation negatively regulates Sec4p function by disrupting the interaction with the exocyst complex via Sec15p. We demonstrate that phosphorylation of Sec4p is a cell cycle-dependent process associated with cytokinesis. Through a genomic kinase screen, we have also identified the polo-like kinase Cdc5p as a positive regulator of Sec4p phosphorylation. Sec4p spatially and temporally localizes with Cdc5p exclusively when Sec4p phosphorylation levels peak during the cell cycle, indicating Sec4p is a direct Cdc5p substrate. Our data suggest the physiological relevance of Sec4p phosphorylation is to facilitate the coordination of membrane-trafficking events during cytokinesis.

Eight-Year Experience With Botulinum Toxin Type-A Injections for the Treatment of Nonneurogenic Overactive Bladder: Are Repeated Injections Worthwhile?

PURPOSE: To investigate the efficacy and safety of repeated botulinum toxin type-A (BTX-A) injections for patients with drug-refractory nonneurogenic overactive bladder (NNOAB) and explore factors predictive of outcome. METHODS: Data were collected from all patients receiving repeated BTX-A injections for drug-refractory NNOAB between 2004 and 2012. Trigone-sparing injections were administered under sedation with antibiotic prophylaxis. Patient characteristics including age, sex, preoperative urodynamics, injection number, BTX-A dose, complications, and patient global impression of improvement (PGI-I) scores were collected. Correlations between patient factors and outcomes were assessed by using Pearson's chi-square tests. RESULTS: Fifty-two patients with a mean age of 67.4 years (range, 26-93 years) received 140 BTX-A injections in total; 33 (64%), 15 (29%), and 4 patients (7%) received 2, 3 to 4, and 5 to 8 injections, respectively. Mean follow-up time was 49 months (range, 9-101 months). Nine patients developed urinary tract infection; additionally, 3 patients experienced transient urinary retention. Median PGI-I score was 2 out of 7 (interquartile range [IQR], 2). For 46 patients, the PGI-I score remained stable with the administration of each injection. Pearson chi-square tests revealed that male patients or reduced bladder compliance was associated with a higher (worse) PGI-I score. Median PGI-I scores for men and women were 3 (IQR, 1) and 2 (IQR, 1), respectively; additionally, median PGI-I scores for those with normal bladder compliance and those with reduced bladder compliance were 2 (IQR, 2) and 4.5 (IQR, 1), respectively. Median PGI-I scores and complication rates were the same in the older patient (≥70 years) and younger (<70 years) patient cohorts. CONCLUSIONS: Efficacy is maintained with repeated BTX-A injections. Patients including the elderly show a good degree of tolerability with a low complication rate. Male patients or reduced bladder compliance is associated with poorer outcomes.

New insights into the molecular mechanism of the Rab GTPase Sec4p activation.

BACKGROUND: Sec4p is a small monomeric Ras-related GTP-binding protein (23 kDa) that regulates polarized exocytosis in S. cerevisiae. In this study we examine the structural effects of a conserved serine residue in the P-loop corresponding to G12 in Ras. RESULTS: We show that the Sec4p residue serine 29 forms a hydrogen bond with the nucleotide. Mutations of this residue have a different impact than equivalent mutations in Ras and can form stable associations with the exchange factor allowing us to elucidate the structure of a complex of Sec4p bound to the exchange factor Sec2p representing an early stage of the exchange reaction. CONCLUSIONS: Our structural investigation of the Sec4p-Sec2p complex reveals the role of the Sec2p coiled-coil domain in facilitating the fast kinetics of the exchange reaction. For Ras-family GTPases, single point mutations that impact the signaling state of the molecule have been well described however less structural information is available for equivalent mutations in the case of Rab proteins. Understanding the structural properties of mutants such as the one described here, provides useful insights into unique aspects of Rab GTPase function.

Botulinum toxin (OnabotulinumtoxinA) in the male non-neurogenic overactive bladder: clinical and quality of life outcomes.

OBJECTIVE: To assess the efficacy of OnabotulinumtoxinA (BTXA) injections in men with drug-refractory non-neurogenic overactive bladder (NNOAB). PATIENTS AND METHODS: A total of 43 men received BTXA injections for NNOAB from 2004 to 2012. Patient Global Impression of Improvement (PGI-I) score was obtained. For men with wet NNOAB, change in number of pads per day was also assessed. RESULTS: Forty-three men with a mean age of 69 (range 37-85) received at least one injection. Of the 43 men, 20 (47%) had prior prostate surgery: 11 had radical prostatectomy (RP) and nine had transurethral resection of prostate (TURP). Overall, average PGI-I score was 2.7. Comparing PGI-I score in men who had prior prostate surgery with men who have not: 2.6 ± 0.5 vs 2.8 ± 0.5 respectively (average ± 95% CI), P = 0.6. Comparing PGI-I score in men who had previous TURP with men who had previous RP: PGI-I score: 3.3 ± 0.8 vs 2.0 ± 0.5 respectively, P < 0.05. Men who had RP experienced a reduction in pad use (from 3.5 ± 1.7 to 1.6 ± 0.9 pads/day, P < 0.05) while this was not the case amongst men who had TURP (from 1.7 ± 1.5 to 1.4 ± 1.5 pads/day, P = 0.4). CONCLUSION: Overall, BTXA injection in men with drug-refractory NNOAB does provide a symptomatic benefit. Amongst men who have had prior prostate surgery, men who have had RP experience a greater benefit than men who have had TURP, both in regards to PGI-I score and pad use.

A lysine deacetylase Hos3 is targeted to the bud neck and involved in the spindle position checkpoint.

An increasing number of cellular activities can be regulated by reversible lysine acetylation. Targeting the enzymes responsible for such posttranslational modifications is instrumental in defining their substrates and functions in vivo. Here we show that a Saccharomyces cerevisiae lysine deacetylase, Hos3, is asymmetrically targeted to the daughter side of the bud neck and to the daughter spindle pole body (SPB). The morphogenesis checkpoint member Hsl7 recruits Hos3 to the neck region. Cells with a defect in spindle orientation trigger Hos3 to load onto both SPBs. When associated symmetrically with both SPBs, Hos3 functions as a spindle position checkpoint (SPOC) component to inhibit mitotic exit. Neck localization of Hos3 is essential for its symmetric association with SPBs in cells with misaligned spindles. Our data suggest that Hos3 facilitates cross-talk between the morphogenesis checkpoint and the SPOC as a component of the intricate monitoring of spindle orientation after mitotic entry and before commitment to mitotic exit.

Techniques to aid the implementation of novel clinical information systems: a systematic review.

BACKGROUND: This systematic review identifies and evaluates techniques that aid the implementation of novel clinical information systems (CIS) within healthcare. METHODS: We searched electronic databases (MEDLINE, EMBASE, PsycINFO and HMIC Health Management Information Consortium). Desktop reviews for all potentially eligible studies were also conducted via reference lists and forward citation searches. 14,198 abstracts were identified through the initial electronic search. 63 articles were retained following title and abstract reviews, and submitted for full text evaluation. Of these, 18 papers met eligibility criteria. RESULTS: The 5 techniques that emerged from the review and that can assist CIS implementation were: system piloting, eliciting acceptance, use of simulation, training and education, and provision of incentives. These techniques were evaluated with a range of study endpoints (including system utilisation, clinical effectiveness, user satisfaction, attitudes towards system training, and attitudes towards implementation). Consideration of the clinical context in which the CIS was implemented was a consistent theme in the evidence-base. CONCLUSIONS: Although some evidence is available for the effectiveness of the 5 implementation techniques found in this review, the variable endpoints and the non-comparable study designs mean that the evidence-base needs further developing. We discuss the potential role of simulation and clinical leadership, particularly in relation to surgeons, in CIS implementation and we propose practical advice for CIS implementation and evaluation within hospital settings.

Clinical information transfer and data capture in the acute myocardial infarction pathway: an observational study.

RATIONALE, AIMS AND OBJECTIVES: Acute myocardial infarctions (MIs) or heart attacks are the result of a complete or an incomplete occlusion of the lumen of the coronary artery with a thrombus. Prompt diagnosis and early coronary intervention results in maximum myocardial salvage, hence time to treat is of the essence. Adequate, accurate and complete information is vital during the early stages of admission of an MI patient and can impact significantly on the quality and safety of patient care. This study aimed to record how clinical information between different clinical teams during the journey of a patient in the MI care pathway is captured and to review the flow of information within this care pathway. METHOD: A prospective, descriptive, structured observational study to assess (i) current clinical information systems (CIS) utilization and (ii) real-time information availability within an acute cardiac care setting was carried out. Completeness and availability of patient information capture across four key stages of the MI care pathway were assessed prospectively. RESULTS: Thirteen separate information systems were utilized during the four phases of the MI pathway. Observations revealed fragmented CIS utilization, with users accessing an average of six systems to gain a complete set of patient information. Data capture was found to vary between each pathway stage and in both patient cohort risk groupings. The highest level of information completeness (100%) was observed only in the discharge stage of the MI care pathway. The lowest level of information completeness (58%) was observed in the admission stage. CONCLUSION: The study highlights fragmentation, CIS duplication, and discrepancies in the current clinical information capture and data transfer across the MI care pathway in an acute cardiac care setting. The development of an integrated and user-friendly electronic data capture and transfer system would reduce duplication and would facilitate efficient and complete information provision at the point of care.

The use of skilled strategies in social interactions by groups high and low in self-reported social skill.

Individuals high or low in self-reported social skill were recruited opportunistically. When presented with everyday social scenarios ending with an awkward request or offer, the high social skill participants more often used sophisticated strategies that showed greater consideration for all parties. By contrast, the low skill participants were more reliant on simple strategies including acquiescence or refusal, and the emotional tone of their responses was less positive. Greater reliance on sophisticated rather than simple strategies may be linked to more successful social interactions. The potential implications are considered for understanding everyday performance in skilled individuals and populations with limited social skills, such as those with autistic spectrum disorders.

Phosphorylation provides a negative mode of regulation for the yeast Rab GTPase Sec4p.

The Rab family of Ras-related GTPases are part of a complex signaling circuitry in eukaryotic cells, yet we understand little about the mechanisms that underlie Rab protein participation in such signal transduction networks, or how these networks are integrated at the physiological level. Reversible protein phosphorylation is widely used by cells as a signaling mechanism. Several phospho-Rabs have been identified, however the functional consequences of the modification appear to be diverse and need to be evaluated on an individual basis. In this study we demonstrate a role for phosphorylation as a negative regulatory event for the action of the yeast Rab GTPase Sec4p in regulating polarized growth. Our data suggest that the phosphorylation of the Rab Sec4p prevents interactions with its effector, the exocyst component Sec15p, and that the inhibition may be relieved by a PP2A phosphatase complex containing the regulatory subunit Cdc55p.

Emotional impact of screening: a systematic review and meta-analysis.

BACKGROUND: There is a widely held expectation that screening for disease has adverse emotional impacts. The aim of the current review is to estimate the short (< 4 weeks) and longer term (> 4 weeks) emotional impact of such screening. METHODS: Studies selected for inclusion were (a) randomised controlled trials in which (b) participants in one arm underwent screening and received test results, and those in a control arm did not, and (c) emotional outcomes were assessed in both arms. MEDLINE via PubMed (1950 to present), EMBASE (1980 to present), PsycINFO (1985 to present) using OVID SP, and CINAHL (1982 to present) via EBSCO were searched, using strategies developed with keywords and medical subject headings. Data were extracted on emotional outcomes, type of screening test and test results. RESULTS: Of the 12 studies that met the inclusion criteria, six involved screening for cancer, two for diabetes, and one each for abdominal aortic aneurysms, peptic ulcer, coronary heart disease and osteoporosis. Five studies reported data on anxiety, five [corrected] on depression, two on general distress and eight on quality of life assessed between one week and 13 years after screening (median = 1.3 years).Meta-analyses revealed no significant impact of screening on longer term anxiety (pooled SMD 0.01, 95% CI -0.10, 0.11), depression (pooled SMD -0.04, 95% CI -.12, 0.20), or quality of life subscales (mental and self-assessed health pooled SMDs, respectively: 0.03; -0.01, (95% CI -.02, 0.04; 0.00, 95% CI -.04, 0.03). CONCLUSION: Screening does not appear to have adverse emotional impacts in the longer term (> 4 weeks). Too few studies assessed outcomes before four weeks to comment on the shorter term emotional impact of screening.

Impact of communicating personalized genetic risk information on perceived control over the risk: a systematic review.

PURPOSE: Much concern has been expressed that feedback of personalized genetic risk information may lead to fatalism, i.e., a lack of perceived control over the risk. This review aimed to assess the strength of evidence for such a view. METHOD: Electronic databases were searched to find eligible studies, which comprised randomized, controlled trials and analog studies, in which participants in one arm received either real or imagined personalized genetic risk information and assessed perceived control in relation to the treatability or preventability of the health problem. RESULTS: Inspection of 1340 abstracts resulted in 5 studies meeting the inclusion criteria, involving the prediction of obesity, heart disease, depression, and diabetes. Meta-analyses of the clinical studies revealed no impact of personalized genetic risk information on perceived control in either the short term (pooled standardized mean difference 0.09, 95% confidence interval, -0.51 to 0.70) or longer term (pooled standardized mean difference 0.00, confidence interval, -0.20 to 0.21). Similarly, no impact on perceived control was evident in the three analog studies (pooled standardized mean difference 0.02, confidence interval, -0.17 to 0.20). CONCLUSION: Few studies have assessed empirically the impact of personalized genetic risk information on fatalism, assessed using perceptions of control over the risk. Limited evidence suggests feedback of genetic risk information may have little impact on such beliefs.

Efficacy of treatment in an opioid -dependent population group using the Maudsley Addiction Profile (MAP) tool.

A pilot study was performed to assess the effectiveness of treatment in an opioid dependent population using the Maudsley Addiction Profile (MAP) tool1.The primary outcome of the study was to assess if treatment had an effect on 1. Substance use (quantity and frequency of use), 2. Health risk behaviour (injecting and sharing injecting equipment), 3. Health symptoms (physical and psychological) and 4. Personal /Social functioning (relationships, employment and crime). A secondary outcome was also sought.The study took place in 2007 in an inner city Belfast hospital specialising in the treatment of addiction, over a two month period. Fifteen patients, all opioid dependent and receiving outpatient community treatment, were interviewed at baseline (prior to the commencement of treatment) and at eight weeks follow up.Three patients were lost to follow up. Two patients stopped using altogether. Of the remaining patients, improvements were seen in most areas. There was a decrease in the use of heroin (71.28%), cocaine (99.72%), crack cocaine (100%), cannabis (99.94%) and alcohol (33.17%). There was a reduction in injecting behaviour (60.93%). Improvements were observed in health with a reduction in physical (41.35%) and psychological (35%) symptoms. Overall personal and social functioning improved regarding interactions with family and friends. A reduction in crime was also observed (75%).Opinions and views of staff involved in the study were generally positive.This patient population presents with multiple and complex needs. Effective treatment needs to address these needs and not just drug addiction alone. The Maudsley Addiction Profile tool highlights this.