UBC-Nepal Expedition: Acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea-level and high-altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g. shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA

UBC-Nepal Expedition: Acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea-level and high-altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g. shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Quality of antimalarial drugs and antibiotics in Papua New Guinea: A survey of the health facility supply chain

Background: Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG.Methods and Findings: Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions.Conclusions: This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing

The role of Comprehension in Requirements and Implications for Use Case Descriptions

Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

Community based weighing of newborns and use of mobile phones by village elders in rural settings in Kenya: a decentralised approach to health care provision

<p>Abstract</p> <p>Background</p> <p>Identifying every pregnancy, regardless of home or health facility delivery, is crucial to accurately estimating maternal and neonatal mortality. Furthermore, obtaining birth weights and other anthropometric measurements in rural settings in resource limited countries is a difficult challenge. Unfortunately for the majority of infants born outside of a health care facility, pregnancies are often not recorded and birth weights are not accurately known. Data from the initial 6 months of the Maternal and Neonatal Health (MNH) Registry Study of the Global Network for Women and Children's Health study area in Kenya revealed that up to 70% of newborns did not have exact weights measured and recorded by the end of the first week of life; nearly all of these infants were born outside health facilities.</p> <p>Methods</p> <p>To more completely obtain accurate birth weights for all infants, regardless of delivery site, village elders were engaged to assist in case finding for pregnancies and births. All elders were provided with weighing scales and mobile phones as tools to assist in subject enrollment and data recording. Subjects were instructed to bring the newborn infant to the home of the elder as soon as possible after birth for weight measurement.</p> <p>The proportion of pregnancies identified before delivery and the proportion of births with weights measured were compared before and after provision of weighing scales and mobile phones to village elders. Primary outcomes were the percent of infants with a measured birth weight (recorded within 7 days of birth) and the percent of women enrolled before delivery.</p> <p>Results</p> <p>The recorded birth weight increased from 43 ± 5.7% to 97 ± 1.1. The birth weight distributions between infants born and weighed in a health facility and those born at home and weighed by village elders were similar. In addition, a significant increase in the percent of subjects enrolled before delivery was found.</p> <p>Conclusions</p> <p>Pregnancy case finding and acquisition of birth weight information can be successfully shifted to the community level.</p

Cleft Lip with Cleft Palate, Ankyloglossia, and Hypodontia are Associated with TBX22 Mutations

X-linked cleft palate and ankyloglossia (CPX) are caused by mutations in the TBX22 transcription factor. To investigate whether patients with ankyloglossia alone or in the presence of other craniofacial features including hypodontia or CLP might be caused by TBX22 mutations, we analyzed 45 Thai patients with isolated ankyloglossia, 2 unusual CPA families, and 282 non-syndromic Thai and UK patients with CLP. Five putative missense mutations were identified, including 3 located in the T-box binding domain (R120Q, R126W, and R151L) that affects DNA binding and/or transcriptional repression. The 2 novel C-terminal mutations, P389Q and S400Y, did not affect TBX22 activity. Mutations R120Q and P389Q were identified in patients with ankyloglossia only, while R126W and R151L were present in families that included CLP. Several individuals in these families were also found to have micro/hypodontia. This study has expanded the phenotypic spectrum of TBX22-related mutations to include dental anomalies and cleft lip

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /