Investigation Into the Humaneness of Slaughter Methods for Guinea Pigs (Cavia porcelus) in the Andean Region

Guinea pigs (Cavia porcelus) are an important source of nonhuman animal protein in the Andean region of South America. Specific guidelines regarding the welfare of guinea pigs before and during slaughter have yet to be developed. This study critically assessed the humaneness of 4 different stunning/slaughter methods for guinea pigs: cervical neck dislocation (n = 60), electrical head-only stunning (n = 83), carbon dioxide (CO(2)) stunning (n = 21), and penetrating captive bolt (n = 10). Following cervical neck dislocation, 97% of guinea pigs had at least 1 behavioral or cranial/spinal response. Six percent of guinea pigs were classified as mis-stunned after electrical stunning, and 1% were classified as mis-stunned after captive bolt. Increased respiratory effort was observed during CO(2) stunning. Apart from this finding, there were no other obvious behavioral responses that could be associated with suffering. Of the methods assessed, captive bolt was deemed the most humane, effective, and practical method of stunning guinea pigs. Cervical neck dislocation should not be recommended as a slaughter method for guinea pigs

Yellow Fever Outbreak, Southern Sudan, 2003

In May 2003, an outbreak of fatal hemorrhagic fever, caused by yellow fever virus, occurred in southern Sudan. Phylogenetic analysis showed that the virus belonged to the East African genotype, which supports the contention that yellow fever is endemic in East Africa with the potential to cause large outbreaks in humans

Modeled Effect of Coastal Biogeochemical Processes, Climate Variability, and Ocean Acidification on Aragonite Saturation State in the Bering Sea

The Bering Sea is highly vulnerable to ocean acidification (OA) due to naturally cold, poorly buffered waters and ocean mixing processes. Harsh weather conditions within this rapidly changing, geographically remote environment have limited the quantity of carbon chemistry data, thereby hampering efforts to understand underlying spatial-temporal variability and detect long-term trends. We add carbonate chemistry to a regional biogeochemical model of the Bering Sea to explore the underlying mechanisms driving carbon dynamics over a decadal hindcast (2003–2012). The results illustrate that coastal processes generate considerable spatial variability in the biogeochemistry and vulnerability of Bering Sea shelf water to OA. Substantial seasonal biological productivity maintains high supersaturation of aragonite on the outer shelf, whereas riverine freshwater runoff loaded with allochthonous carbon decreases aragonite saturation states (ΩArag) to values below 1 on the inner shelf. Over the entire 2003–2012 model hindcast, annual surface ΩArag decreases by 0.025 – 0.04 units/year due to positive trends in the partial pressure of carbon dioxide (pCO2) in surface waters and dissolved inorganic carbon (DIC). Variability in this trend is driven by an increase in fall phytoplankton productivity and shelf carbon uptake, occurring during a transition from a relatively warm (2003–2005) to cold (2010–2012) temperature regime. Our results illustrate how local biogeochemical processes and climate variability can modify projected rates of OA within a coastal shelf system

Phylogenetic Relationships of Southern African West Nile Virus Isolates

Phylogenetic relationships were examined for 29 southern African West Nile virus (formal name West Nile virus [WNV]) isolates from various sources in four countries from 1958 to 2001. In addition sequence data were retrieved from GenBank for another 23 WNV isolates and Kunjin and Japanese encephalitis viruses. All isolates belonged to two lineages. Lineage 1 isolates were from central and North Africa, Europe, Israel, and North America; lineage 2 isolates were from central and southern Africa and Madagascar. No strict correlation existed between grouping and source of virus isolate, pathogenicity, geographic distribution, or year of isolation. Some southern African isolates have been associated with encephalitis in a human, a horse, and a dog and with fatal hepatitis in a human and death of an ostrich chick

Impact of Carotid Artery Stenosis on Quality of Life: A Systematic Review

© 2018, Springer Nature Switzerland AG. Objectives: The aim of this study was to identify themes that determine health-related quality of life (HRQoL) in patients with carotid artery stenosis and identify the patient-reported outcome measures (PROMs) that best cover the identified themes. Methods: A systematic review of the main six databases from inception to September 2018 was undertaken to identify primary qualitative studies reporting on the HRQoL of patients with carotid artery stenosis. The quality of studies was assessed using the Critical Appraisal Skills Programme (CASP) criteria. Findings from the included studies were analysed using framework analysis methodology. The identified themes were mapped against the items/domains from the PROMs used previously in patients with carotid artery stenosis. Results: The systematic review identified four papers that fulfilled the inclusion criteria. The included papers reported the views of 62 patients with symptomatic carotid artery stenosis; 24 of the patients were awaiting assessment for intervention, 26 had carotid endarterectomy, and 12 were turned down for intervention and received best medical therapy. The overall quality of the included studies was good based on CASP criteria. Framework analysis identified 16 themes that were divided into five main domains: anxiety, impact on personal roles and activities, effect on independence, psychological impact, and symptoms. The best-fit generic and disease-specific PROMs were the Medical Outcomes Study 36-Item Short Form (SF-36®) and the Carotid Stenosis Specific Outcome Measure (CSSOM), respectively. None of the PROMs covered all the themes identified in the qualitative systematic review. Conclusion: The findings from the review identified the important themes that affect patients with carotid stenosis disease. The current generic and disease-specific PROMs do not cover all themes that impact the HRQoL of patients suffering with this disease. The proposed themes can be used to develop a new disease-specific PROM to measure HRQoL

Themes that Determine Quality of Life in Patients with Peripheral Arterial Disease: A Systematic Review

© 2018 Springer International Publishing AG, part of Springer Nature Objectives: The aim of this study was to identify domains that determine quality of life in patients with peripheral arterial disease and find the patient-reported outcome measures that can examine the identified themes. Methods: A systematic review of all the main six databases was undertaken to identify primary qualitative studies reporting on the health and/or quality of life of patients with peripheral arterial disease. The quality of studies was assessed using the Critical Appraisal Skills Program criteria. Findings from the included studies were analysed using framework analysis methodology. The identified themes were mapped against the items/domains of validated patient-reported outcome measures used in patients with peripheral arterial disease. Results: The systematic review identified eight papers that fulfilled the inclusion criteria. The included papers reported the views of 186 patients with peripheral arterial disease including patients with intermittent claudication, critical ischaemia and amputation secondary to peripheral arterial disease. The overall quality of the included studies was good based on Critical Appraisal Skills Program criteria. Framework analysis identified 35 themes that were divided into six main groups: symptoms, impact on physical functioning, impact on social functioning, psychological impact, financial impact and process of care. The best-fit generic and disease-specific patient-reported outcome measures were the Nottingham Health Profile and the Vascular Quality of Life Questionnaire, respectively. None of the patient-reported outcome measures covered all the themes important to patients with peripheral arterial disease. Discussion: The findings from the review identified the important domains that affect patients living with peripheral arterial disease. None of the current generic and disease-specific patient-reported outcome measures provide a comprehensive measure for all themes that impact the daily living of patients with peripheral arterial disease

A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias

Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the ‘discoverability’ of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family

Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991-2019.

BACKGROUND: Anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. METHODS: This study uses data from 232 efficacy trials comprised of 86,776 infected individuals to estimate the artemisinin-based and non-artemisinin-based AmE for treating falciparum malaria between 1991 and 2019. Bayesian spatiotemporal models were fitted and used to predict effectiveness at the pixel-level (5 km × 5 km). The median and interquartile ranges (IQR) of AmE are presented for all malaria-endemic countries. RESULTS: The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3-75.8), 70.1% (43.6-76.0) and 71.8% (46.9-76.4) for the 1991-2000, 2006-2010, and 2016-2019 periods, respectively. Countries in central Africa, a few in South America, and in the Asian region faced the challenge of lower effectiveness of artemisinin-based anti-malarials. However, improvements were seen after 2016, leaving only a few hotspots in Southeast Asia where resistance to artemisinin and partner drugs is currently problematic and in the central Africa where socio-demographic challenges limit effectiveness. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based with no improvement over time: 52.3% (17.9-74.9) for 1991-2000 and 55.5% (27.1-73.4) for 2011-2015. Overall, AmE for artemisinin-based and non-artemisinin-based drugs were, respectively, 29.6 and 36% below clinical efficacy as measured in anti-malarial drug trials. CONCLUSIONS: This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries' treatment practises and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead