Schematics of a Water Balloon Launcher Design and Reproducible Water-Balloon-Filling Procedures Used for a Middle School Summer Science Camp

We recently held a Science Summer Camp for middle school students, designed to infuse young people with increased excitement for STEM (Science, Technology, Engineering, and Math) subjects. Our efforts, which received nationally-syndicated news coverage,1 included the invention of a versatile water balloon launcher. This document contains: (1) detailed construction schematics and user operation guidelines for our balloon launcher; (2) data and instructions for reproducibly filling water balloons to specific volumes and weights, within used by students during the summer camp

The metformin in tuberous sclerosis (MiTS) study:A randomised double-blind placebo-controlled trial

Background: Tuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex. / Methods: In this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30. / Findings: Between 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (p = 0.28). Twenty-seven patients had SEGAs: 13 received placebo and 14 metformin. The median percentage change in SEGA volume was +3.0% (IQR -22.8% to +27.7%) for the placebo group and – 20.8% (IQR – 47.1% to - 5.0%) for the metformin group (p = 0.03). Twenty-one patients were assessed for seizure frequency: 9 received placebo and 12 received metformin. In the metformin group, a mean reduction of 43.7% from baseline in seizures was observed and in the placebo group a 3.1% mean reduction was observed, with a difference in response of 40.6% (95% CI -3.1% to +84.2%, p = 0.03). There were no significant differences between metformin and placebo groups for the other secondary outcomes. There were no deaths. Three serious adverse events (SAEs) occurred during the trial (all patients on metformin). / Interpretation: Metformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified. / Funding: This study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB)

Shallow-water benthic habitats of southwest Puerto Rico

This report describes the creation and assessment of benthic habitat maps for shallow-water (<30m) marine environments of the Guánica/Parguera and Finca Belvedere Natural Reserve in southwest Puerto Rico. The objective was to provide spatially-explicit information on the habitat types, biological cover and live coral cover of the region’s coral reef ecosystem. These fine-scale habitat maps, generated by interpretation of 2010 satellite imagery, provide an update to NOAA’s previous digital maps of the U.S. Caribbean (Kendall et al., 2001) for these areas. Updated shallow-water benthic habitat maps for the Guánica/Parguera region are timely in light of ongoing restoration efforts in the Guánica Bay watershed. The bay is served directly by one river, the Rio Loco, which flows intermittently and more frequently during the rainy season. The watershed has gone through a series of manipulations and alterations in past decades, mainly associated with agricultural practices, including irrigation systems, in the upper watershed. The Guánica Lagoon, previously situated to the north of the bay, was historically the largest freshwater lagoon in Puerto Rico and served as a natural filter and sediment sink prior to the discharge of the Rio Loco into the Bay. Following alterations by the Southwest Water Project in the 1950s, the Lagoon’s adjacent wetland system was ditched and drained; no longer filtering and trapping sediment from the Rio Loco. Land use in the Guánica Bay/Rio Loco watershed has also gone through several changes (CWP, 2008). Similar to much of Puerto Rico, the area was largely deforested for sugar cane cultivation in the 1800s, although reforestation of some areas occurred following the cessation of sugar cane production (Warne et al., 2005). The northern area of the watershed is generally mountainous and is characterized by a mix of forested and agricultural lands, particularly coffee plantations. Closer to the coast, the Lajas Valley Agricultural Reserve extends north of Guánica Bay to the southwest corner of the island. The land use practices and watershed changes outlined above have resulted in large amounts of sediment being distributed in the Rio Loco river valley (CWP, 2008). Storm events and seasonal flooding also transport large amounts of sediment to the coastal waters. The threats of upstream watershed practices to coral reefs and the nearshore marine environment have been gaining recognition. Guánica Bay, and the adjacent marine waters, has been identified as a “management priority area” by NOAA’s Coral Reef Conservation Program (CRCP, 2012). In a recent Guánica Bay watershed management plan, several critical issues were outlined in regards to land-based sources of pollution (LBSP; CWP, 2008). These include: upland erosion from coffee agriculture, filling of reservoirs with sediment, in-stream channel erosion, loss of historical Guánica lagoon, legacy contaminants and sewage treatment (CWP, 2008). The plan recommended several management actions that could be taken to reduce impacts of LBSP, which form the basis of Guánica watershed restoration efforts

Building democracy from below : lessons from Western Uganda

How to achieve democratisation in the neopatrimonial and agrarian environments that predominate in sub-Saharan Africa continues to present a challenge for both development theory and practice. Drawing on intensive fieldwork in Western Uganda, this paper argues that Charles Tilly’s ‘democratisation as process’ provides us with the framework required to explain the ways in which particular kinds of association can advance democratisation from below. Moving beyond the current focus on how elite-bargaining and certain associational forms may contribute to liberal forms of democracy, this approach helps identify the intermediate mechanisms involved in building democracy from below, including the significance of challenging categorical inequalities, notably through the role of producer groups, and of building trust networks, cross-class alliances and synergistic relations between civil and political society. The evidence and mode of analysis deployed here help suggest alternative routes for supporting local efforts to build democracy from below in sub-Saharan Africa

Validity of energy expenditure estimation methods during 10 days of military training

Wearable physical activity (PA) monitors have improved the ability to estimate free-living total energy expenditure (TEE) but their application during arduous military training alongside more well-established research methods has not been widely documented. This study aimed to assess the validity of two wrist-worn activity monitors and a PA log against doubly-labelled water (DLW) during British Army Officer Cadet (OC) training. For 10 days of training, twenty (10 male and 10 female) OCs (mean ± SD: age 23 ± 2 years, height 1.74 ± 0.09 m, body mass 77.0 ± 9.3 kg) wore one research-grade accelerometer (GENEActiv, Cambridge, UK) on the dominant wrist, wore one commercially-available monitor (Fitbit SURGE, USA) on the non-dominant wrist and completed a self-report PA log. Immediately prior to this 10-day period, participants consumed a bolus of DLW and provided daily urine samples, which were analysed by mass spectrometry to determine TEE. Bivariate correlations and limits of agreement (LoA) were employed to compare TEE from each estimation method to DLW. Average daily TEE from DLW was 4112 ± 652 kcal·day against which the GENEActiv showed near identical average TEE (mean bias ± LoA: -15 ± 851 kcal day ) while Fitbit tended to underestimate (-656 ± 683 kcal·day ) and the PA log substantially overestimate (+1946 ± 1637 kcal·day ). Wearable physical activity monitors provide a cheaper and more practical method for estimating free-living TEE than DLW in military settings. The GENEActiv accelerometer demonstrated good validity for assessing daily TEE and would appear suitable for use in large-scale, longitudinal military studies

Effects of serelaxin in patients admitted for acute heart failure:a meta-analysis

Aims: The effectiveness and safety of 48 h intravenous 30 μg/kg/day serelaxin infusion in acute heart failure (AHF) has been studied in six randomized, controlled clinical trials. Methods and results: We conducted a fixed-effect meta-analysis including all studies of intravenous serelaxin initiated within the first 16 h of admission for AHF. Endpoints considered were the primary and secondary endpoints examined in the serelaxin phase III studies. In six randomized controlled trials, 6105 total patients were randomized to receive intravenous serelaxin 30 μg/kg/day and 5254 patients to control. Worsening heart failure to day 5 occurred in 6.0% and 8.1% of patients randomized to serelaxin and control, respectively (hazard ratio 0.77, 95% confidence interval 0.67–0.89; P = 0.0002). Serelaxin had no statistically significant effect on length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration resulted in statistically significant improvement in markers of renal function and reductions in both N-terminal pro-B-type natriuretic peptide and troponin. No significant adverse outcomes were noted with serelaxin. Through the last follow-up, which occurred at an average of 4.5 months (1–6 months), serelaxin administration was associated with a reduction in all-cause mortality, with an estimated hazard ratio of 0.87 (95% confidence interval 0.77–0.98; P = 0.0261). Conclusions: Administration of intravenous serelaxin to patients admitted for AHF was associated with a highly significant reduction in the risk of 5-day worsening heart failure and in changes in renal function markers, but not length of stay, or cardiovascular death, or heart or renal failure rehospitalization. Serelaxin administration was safe and associated with a significant reduction in all-cause mortality.</p

International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

Community-facility linkage models and maternal and infant health outcomes in Malawi’s PMTCT/ART program: a cohort study

Background: In sub-Saharan Africa, 3 community-facility linkage (CFL) models—Expert Clients, Community Health Workers (CHWs), and Mentor Mothers—have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. Methods and findings: We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant “poor outcome” (encompassing documented HIV-positive test result, LTFU, or death), in Malawi’s PMTCT/ART program. We sampled 30 of 42 high-volume health facilities (“sites”) in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother–infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother–infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. Conclusions: In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences