Domestic dog health worsens with socio-economic deprivation of their home communities

Dogs play an important role in infectious disease transmission as reservoir hosts of many zoonotic and wildlife pathogens. Nevertheless, unlike wildlife species involved in the life cycle of pathogens, whose health status might be a direct reflection of their fitness and competitive abilities, dog health condition could be sensitive to socio-economic factors impacting the well-being of their owners. Here, we compare several dog health indicators in three rural communities of Panama with different degrees of socio-economic deprivation. From a total of 78 individuals, we collected blood and fecal samples, and assessed their body condition. With the blood samples, we performed routine hematologic evaluation (complete blood counts) and measured cytokine levels (Interferon-γ and Interleukin-10) through enzyme-linked immunosorbent assays. With the fecal samples we diagnosed helminthiases. Dogs were also serologically tested for exposure to Trypanosoma cruzi and canine distemper virus, and molecular tests were done to assess T. cruzi infection status. We found significant differences between dog health measurements, pathogen prevalence, parasite richness, and economic status of the human communities where the dogs lived. We found dogs that were less healthy, more likely to be infected with zoonotic pathogens, and more likely to be seropositive to canine distemper virus in the communities with lower economic status. This study concludes that isolated communities of lower economic status in Panama may have less healthy dogs that could become major reservoirs in the transmission of diseases to humans and sympatric wildlife

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Genetic control of immunity to Trichinella spiralis: influence of H-2-linked genes on immunity to the intestinal phase of infection

The time course of expulsion of adult Trichinella spiralis from the intestine was determined in B10 background, H-2 congenic and recombinant mice. Non-H-2 genes exerted the major influence on worm expulsion (i.e. determined rapid or slow response phenotype) but marked time course differences were seen among the slow responder B10 background strains, implying that H-2-linked genes also influence this parameter of immunity. Independent H-2q haplotype mice showed the most rapid expulsion, H-2k and H-2b the slowest. Data from H-2 recombinant mice carrying the q allele suggested that alleles at H-2K loci have a strong influence in immunity, but showed also that H-2D alleles exert a significant modulating effect. The q allele in otherwise susceptible k haplotype mice (B10.AKM) gave increased resistance; the d allele at H-2D in mice carrying the q resistance allele elsewhere [B10.T(6R)] gave decreased resistance. Adoptive transfers using immune mesenteric node lymphocytes (IMLNC) from a series of donors were used to identify how the modulating influence of H-2Dd was expressed in B10.T(6R) mice. IMLNC from this strain transferred immunity to recipients of other (histocompatible) strains, but IMLNC from such strains failed to accelerate expulsion in B10.T(6R) recipients as did homologous B10.T(6R) cells. Two alternative models are proposed to explain these results: either that H-2Dd influences the response of myeloid precursors to lymphocyte-derived factors, and thus the generation of intestinal inflammatory changes necessary for expulsion, or, on the assumption that the generation of intestinal inflammation requires initial cooperation between helper and effector lymphocytes, that H-2Dd is associated with a restricted ability of effector cells to respond to the helpers present in IMLNC

Short lived, dividing cells mediate adoptive transfer of immunity to Trichinella spiralis in mice. II. In vivo characteristics of the cells

The in vivo characteristics of mesenteric lymph node cells (MLNC) capable of mediating the adoptive transfer of immunity to Trichinella spiralis have been examined. Mediator cells were diverted into the peritoneal cavity of infected donor mice following the induction of a peritoneal exudate and its was shown that these were nylon-wool, non-adherent (T) cells. After density gradient separation of [125I]-UdR-labelled MLNC, the fractions that were most effective in transferring immunity were those containing a small proportion of cells but the largest proportion of incorporated activity. Treatment of the donors of MLNC with the mitotic inhibitor vinblastine effectively prevented both the transfer of immunity and increased incorporation of [125I]-UdR characteristic of the mediator population. In vitro irradiation of MLNC failed to affect their ability to transfer immunity. Collectively these findings support the conclusion that mediator cells are T lymphoblasts, and suggest that mediation of immunity is effected directly by this population and not by their progeny

Short lived, dividing cells mediate adoptive transfer of immunity to Trichinella spiralis in mice. II. In vivo characteristics of the cells

The in vivo characteristics of mesenteric lymph node cells (MLNC) capable of mediating the adoptive transfer of immunity to Trichinella spiralis have been examined. Mediator cells were diverted into the peritoneal cavity of infected donor mice following the induction of a peritoneal exudate and its was shown that these were nylon-wool, non-adherent (T) cells. After density gradient separation of [125I]-UdR-labelled MLNC, the fractions that were most effective in transferring immunity were those containing a small proportion of cells but the largest proportion of incorporated activity. Treatment of the donors of MLNC with the mitotic inhibitor vinblastine effectively prevented both the transfer of immunity and increased incorporation of [125I]-UdR characteristic of the mediator population. In vitro irradiation of MLNC failed to affect their ability to transfer immunity. Collectively these findings support the conclusion that mediator cells are T lymphoblasts, and suggest that mediation of immunity is effected directly by this population and not by their progeny