ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats

Immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune-mediated erythrocyte destruction, and adverse consequences of long-term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence-based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors

Factors underlying age-related changes in discrete aiming

Age has a clear impact on one’s ability to make accurate goal-directed aiming movements. Older adults seem to plan slower and shorter-ranged initial pulses towards the target, and rely more on sensory feedback to ensure endpoint accuracy. Despite the fact that these age-related changes in manual aiming have been observed consistently, the underlying mechanism remains speculative. In an attempt to isolate four commonly suggested underlying factors, young and older adults were instructed to make discrete aiming movements under varying speed and accuracy constraints. Results showed that older adults were physically able to produce fast primary submovements and that they demonstrated similar movement-programming capacities as young adults. On the other hand, considerable evidence was found supporting a decreased visual feedback-processing efficiency and the implementation of a play-it-safe strategy in older age. In conclusion, a combination of the latter two factors seems to underlie the age-related changes in manual aiming behaviour

High rates of burnout among maternal health staff at a referral hospital in Malawi: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Burnout among maternal healthcare workers in sub-Saharan Africa may have a negative effect on services provided and efforts to mitigate high maternal mortality rates. In Malawi, research on burnout is limited and no empirical research has been conducted specifically among maternal health staff. Therefore, the aims of the study were to examine the prevalence and degree of burnout reported by healthcare workers who provide antenatal, intrapartum, and postnatal services in a district referral hospital in Malawi; and, to explore factors that may influence the level of burnout healthcare workers experience.</p> <p>Methods</p> <p>In the current cross-sectional study, levels of burnout among staff working in obstetrics and gynaecology at a referral hospital in Malawi were examined, in addition to individual and job characteristics that may be associated with burnout.</p> <p>Results</p> <p>In terms of the three dimensions of burnout, of the 101 participants, nearly three quarters (72%) reported emotional exhaustion, over one third (43%) reported depersonalization while almost three quarters (74%) experienced reduced personal accomplishment.</p> <p>Conclusions</p> <p>Based on these findings, burnout appears to be common among participating maternal health staff and they experienced more burnout than their colleagues working in other medical settings and countries. Further research is needed to identify factors specific to Malawi that contribute to burnout in order to inform the development of prevention and treatment within the maternal health setting.</p

High Affinity Antibodies to Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Malaria

Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as k(d)) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up. This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations

Do Humans Optimally Exploit Redundancy to Control Step Variability in Walking?

It is widely accepted that humans and animals minimize energetic cost while walking. While such principles predict average behavior, they do not explain the variability observed in walking. For robust performance, walking movements must adapt at each step, not just on average. Here, we propose an analytical framework that reconciles issues of optimality, redundancy, and stochasticity. For human treadmill walking, we defined a goal function to formulate a precise mathematical definition of one possible control strategy: maintain constant speed at each stride. We recorded stride times and stride lengths from healthy subjects walking at five speeds. The specified goal function yielded a decomposition of stride-to-stride variations into new gait variables explicitly related to achieving the hypothesized strategy. Subjects exhibited greatly decreased variability for goal-relevant gait fluctuations directly related to achieving this strategy, but far greater variability for goal-irrelevant fluctuations. More importantly, humans immediately corrected goal-relevant deviations at each successive stride, while allowing goal-irrelevant deviations to persist across multiple strides. To demonstrate that this was not the only strategy people could have used to successfully accomplish the task, we created three surrogate data sets. Each tested a specific alternative hypothesis that subjects used a different strategy that made no reference to the hypothesized goal function. Humans did not adopt any of these viable alternative strategies. Finally, we developed a sequence of stochastic control models of stride-to-stride variability for walking, based on the Minimum Intervention Principle. We demonstrate that healthy humans are not precisely “optimal,” but instead consistently slightly over-correct small deviations in walking speed at each stride. Our results reveal a new governing principle for regulating stride-to-stride fluctuations in human walking that acts independently of, but in parallel with, minimizing energetic cost. Thus, humans exploit task redundancies to achieve robust control while minimizing effort and allowing potentially beneficial motor variability

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early