Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries

Background: As malaria prevalence declines in many parts of the world due to widescale control efforts and as drug-resistant parasites begin to emerge, a quantitative understanding of human movement is becoming increasingly relevant to malaria control. However, despite its importance, significant knowledge gaps remain regarding human movement, particularly in sub-Saharan Africa. Methods: A quantitative survey of human movement patterns was conducted in four countries in sub-Saharan Africa: Mali, Burkina Faso, Zambia, and Tanzania, with three to five survey locations chosen in each country. Questions were included on demographic and trip details, malaria risk behaviour, children accompanying travellers, and mobile phone usage to enable phone signal data to be better correlated with movement. A total of 4352 individuals were interviewed and 6411 trips recorded. Results: A cluster analysis of trips highlighted two distinct traveller groups of relevance to malaria transmission: women travelling with children (in all four countries) and youth workers (in Mali). Women travelling with children were more likely to travel to areas of relatively high malaria prevalence in Mali (OR = 4.46, 95 % CI = 3.42–5.83), Burkina Faso (OR = 1.58, 95 % CI = 1.23–1.58), Zambia (OR = 1.50, 95 % CI = 1.20–1.89), and Tanzania (OR = 2.28, 95 % CI = 1.71–3.05) compared to other travellers. They were also more likely to own bed nets in Burkina Faso (OR = 1.77, 95 % CI = 1.25–2.53) and Zambia (OR = 1.74, 95 % CI = 1.34 2.27), and less likely to own a mobile phone in Mali (OR = 0.50, 95 % CI = 0.39–0.65), Burkina Faso (OR = 0.39, 95 % CI = 0.30–0.52), and Zambia (OR = 0.60, 95 % CI = 0.47–0.76). Malian youth workers were more likely to travel to areas of relatively high malaria prevalence (OR = 23, 95 % CI = 17–31) and for longer durations (mean of 70 days cf 21 days, p < 0.001) compared to other travellers. Conclusions: Women travelling with children were a remarkably consistent traveller group across all four countries surveyed. They are expected to contribute greatly towards spatial malaria transmission because the children they travel with tend to have high parasite prevalence. Youth workers were a significant traveller group in Mali and are expected to contribute greatly to spatial malaria transmission because their movements correlate with seasonal rains and hence peak mosquito densities. Interventions aimed at interrupting spatial transmission of parasites should consider these traveller groups

Understanding the relationship between egg- and antigen-based diagnostics of Schistosoma mansoni infection pre- and post-treatment in Uganda.

BACKGROUND: Schistosomiasis is a major socio-economic and public health problem in many sub-Saharan African countries. After large mass drug administration (MDA) campaigns, prevalence of infection rapidly returns to pre-treatment levels. The traditional egg-based diagnostic for schistosome infections, Kato-Katz, is being substituted in many settings by circulating antigen recognition-based diagnostics, usually the point-of-care circulating cathodic antigen test (CCA). The relationship between these diagnostics is poorly understood, particularly after treatment in both drug-efficacy studies and routine monitoring. RESULTS: We created a model of schistosome infections to better understand and quantify the relationship between these two egg- and adult worm antigen-based diagnostics. We focused particularly on the interpretation of "trace" results after CCA testing. Our analyses suggest that CCA is generally a better predictor of prevalence, particularly after treatment, and that trace CCA results are typically associated with truly infected individuals. CONCLUSIONS: Even though prevalence rises to pre-treatment levels only six months after MDAs, our model suggests that the average intensity of infection is much lower, and is probably in part due to a small burden of surviving juveniles from when the treatment occurred. This work helps to better understand CCA diagnostics and the interpretation of post-treatment prevalence estimations

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Belowground DNA-based techniques: untangling the network of plant root interactions

Contains fulltext : 91591.pdf (publisher's version ) (Closed access)7 p

Use of intravenous immunoglobulin for the treatment of autoimmune encephalitis: audit of the NHS experience

OBJECTIVES: The treatments of limbic and other autoimmune encephalitis include immunosuppression, symptomatic treatment, and in the case of paraneoplastic syndromes, appropriate therapy for underlying neoplasms. When immunotherapy is considered, intravenous immunoglobulin is one option for treatment, either alone or in combination with corticosteroids. To date, however, evidence for the use of intravenous immunoglobulin in this context comes from case series/expert reviews as no controlled trials have been performed. We aimed to analyse the NHS England Database of intravenous immunoglobulin usage, which was designed to log use and guide procurement, to explore usage and therapeutic effect of intravenous immunoglobulin in autoimmune encephalitis in England. DESIGN: We conducted a retrospective audit and review of the NHS England Database on intravenous immunoglobulin use. Setting: NHS England Database of intravenous immunoglobulin use which covers secondary and tertiary care prescribing and use of intravenous immunoglobulin for all patients in hospitals in England. PARTICIPANTS: Hospital in-patients with confirmed or suspected autoimmune/limbic encephalitis between September 2010 and January 2017. RESULTS: A total of 625 patients who were 18 years of age or older were treated with intravenous immunoglobulin for autoimmune encephalitis, of whom 398 were determined as having 'highly likely' or 'definite' autoimmune/limbic encephalitis. Ninety-six percent were treated with a single course of intravenous immunoglobulin. The availability and accuracy of reporting of outcomes was very poor, with complete data only available in 27% of all cases. CONCLUSIONS: This is the first review of data from this unique national database. Whilst there was evidence for clinical improvement in many cases of patients treated with intravenous immunoglobulin, the quality of outcome data was generally inadequate. Methods to improve quality, accuracy and completeness of reporting are crucial to maximise the potential value of this resource as an auditing tool

Commentary on the use of the reproduction number R during the COVID-19 pandemic

Since the beginning of the COVID-19 pandemic, the reproduction number R has become a popular epidemiological metric used to communicate the state of the epidemic. At its most basic, R is defined as the average number of secondary infections caused by one primary infected individual. R seems convenient, because the epidemic is expanding if R>1 and contracting if R<1. The magnitude of R indicates by how much transmission needs to be reduced to control the epidemic. Using R in a naïve way can cause new problems. The reasons for this are threefold: (1) There is not just one definition of R but many, and the precise definition of R affects both its estimated value and how it should be interpreted. (2) Even with a particular clearly defined R, there may be different statistical methods used to estimate its value, and the choice of method will affect the estimate. (3) The availability and type of data used to estimate R vary, and it is not always clear what data should be included in the estimation. In this review, we discuss when R is useful, when it may be of use but needs to be interpreted with care, and when it may be an inappropriate indicator of the progress of the epidemic. We also argue that careful definition of R, and the data and methods used to estimate it, can make R a more useful metric for future management of the epidemic

Emergent versus delayed lithotripsy for obstructing ureteral stones: a cumulative analysis of comparative studies

Objective To analyze the current evidence on the use of ureteroscopy (URS) and extracorporeal shock wave lithotripsy (ESWL) for the management of obstructing ureteral stones in emergent setting. Methods A systematic literature review was performed up to June 2016 using Pubmed and Ovid databases to identify pertinent studies. The PRISMA criteria were followed for article selection. Separate searches were done using a combinations of several search terms: "laser lithotripsy", "ureteroscopy", "extracorporeal shock wave lithotripsy", "ESWL", "rapid", "immediate", "early", "delayed", "late", "ureteral stones", "kidney stones", "renal stones". Only titles related to emergent/rapid/immediate/early (as viably defined in each study) versus delayed/late treatment of ureteral stones with either URS and/or ESWL were considered for screening. Demographics and operative outcomes were compared between emergent and delayed lithotripsy. RevMan review manager software was used to perform data analysis. Results Four studies comparing emergent (n = 526) versus delayed (n = 987) URS and six studies comparing emergent (n = 356) versus delayed (n = 355) SWL were included in the analysis. Emergent URS did not show any significant difference in terms of stone-free rate (91.2 versus 90.9%; OR 1.04; CI 0.71, 1.52; p = 0.84), complication rate (8.7% for emergent versus 11.5% for delayed; OR 0.94; CI 0.65, 1.36; p = 0.74) and need for auxiliary procedures (OR 0.85; CI 0.42, 1.7; p = 0.85) when compared to delayed URS. Emergent ESWL was associated with a higher likelihood of stone free status (OR 2.2; CI 1.55, 3.17; p < 0.001) and a lower likelihood of need for auxiliary maneuvers (OR 0.49; CI 0.33, 0.72; p < 0.001) than the delayed procedure. No differences in complication rates were noticed between the emergent and delayed ESWL (p = 0.37). Conclusions Emergent lithotripsy, either ureteroscopic or extracorporeal, can be offered as an effective and safe treatment for patients with symptomatic ureteral stone. If amenable to ESWL, based on stone and patient characteristics, an emergent approach should be strongly considered. Ureteroscopy in the emergent setting is mostly reserved for distally located stones. The implementation of these therapeutic approaches is likely to be dictated by their availability.info:eu-repo/semantics/publishedVersio

Insights from quantitative and mathematical modelling on the proposed WHO 2030 goal for schistosomiasis

Schistosomiasis remains one of the neglected tropical diseases (NTDs) impacting millions of people around the world. The World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. Current WHO treatment guidelines for achieving EPHP focus on targeting school-aged children. The NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures. Our modelling insights on Schistosoma mansoni have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines. However, as prevalence rises within high prevalence settings, EPHP is less likely to be achieved unless both school-aged children and adults are treated (with coverage levels increasing with the adult burden of infection). We highlight the challenges that are faced by treatment programmes, such as non-adherence to treatment and resurgence, which can hinder progress towards achieving and maintaining EPHP. Additionally, even though EPHP may be reached, prevalence can still be high due to persisting infections. Therefore, without interruption of transmission, treatment will likely have to continue to maintain EPHP. Further modelling work is being carried out, including extending our results to S. haematobium. By providing these modelling insights, we aim to inform discussions on the goals and treatment guidelines for schistosomiasis.</ns4:p

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

Retroperitoneoscopic radical nephrectomy with a small incision for renal cell carcinoma: Comparison with the conventional method

<p>Abstract</p> <p>purpose</p> <p>When retroperitoneoscopic radical nephrectomy for renal cell carcinoma was introduced into our institution, we performed a combined small skin incision method. In this method, a small incision was made to approach the retroperitoneal space prior to setting trockers and thereafter a LAPDISC was placed in the incision to start the retroperitoneoscopic procedure. In this study, we compared the outcomes between the combined small skin incision method ("A method" hereinafter) and the conventional method ("B method" hereinafter).</p> <p>material and methods</p> <p>Among the cases of T1N0M0 suspicious renal cell carcinoma treated at Yokohama City University between May 2003 and June 2009, the A method was performed in 51 cases and the B method was performed in 33 cases. The factors in the outcomes compared between the A and B methods were the duration of procedure, volume of bleeding, volume of transfusion, weight of the specimen, incidence of peritoneal injury, rate of conversion to open surgery, and perioperative complications.</p> <p>results</p> <p>The duration of the procedure was 214.4 ± 46.9 minutes in the A method group and 208.1 ± 36.4 minutes in the B method group (p = 0.518). The volume of bleeding and the weight of the specimen were 105.5 ± 283.2 ml and 335.1 ± 137.4 g in the A method group and 44.8 ± 116 ml (p = 0.247) and 309.2 ± 126 g (p = 0.385) in the B method group. There was no significant difference in all factors analyzed.</p> <p>conclusion</p> <p>The A method would be highly possible to produce stable results, even during the introduction period when the staff and the institution are still unfamiliar with the retroperitoneoscopic surgery.</p