Can the use of digital algorithms improve quality care? An example from Afghanistan

Quality of care is a difficult parameter to measure. With the introduction of digital algorithms based on the Integrated Management of Childhood Illness (IMCI), we are interested to understand if the adherence to the guidelines improved for a better quality of care for children under 5 years old.; More than one year after the introduction of digital algorithms, we carried out two cross sectional studies to assess the improvements in comparison with the situation prior to the implementation of the project, in two Basic Health Centres in Kabul province. One survey was carried out inside the consultation room and was based on the direct observation of 181 consultations of children aged 2 months to 5 years old, using a checklist completed by a senior physicians. The second survey queried 181 caretakers of children outside the health facility for their opinion about the consultation carried out through the tablet and prescriptions and medications given.; We measured the quality of care as adherence to the IMCI's guidelines. The study evaluated the quality of the physical examination and the therapies prescribed with a special attention to antibiotic prescription. We noticed a dramatic improvement (p<0.05) of several indicators following the introduction of digital algorithms. The baseline physical examination was appropriate only for 23.8% [IC% 19.9-28.1] of the patients, 34.5% [IC% 30.0-39.2] received a correct treatment and 86.1% [IC% 82.4-89.2] received at least one antibiotic. With the introduction of digital algorithms, these indicators statistically improved respectively to 84.0% [IC% 77.9-88.6], >85% and less than 30%.; Our findings suggest that digital algorithms improve quality of care by applying the guidelines more effectively. Our experience should encourage to test this tool in different settings and to scale up its use at province/state level

Nitrogen balances in farmers fields under alternative uses of a cover crop legume: a case study from Nicaragua

Canavalia brasiliensis (canavalia), a drought tolerant legume, was introduced into the smallholder traditional crop-livestock production system of the Nicaraguan hillsides as green manure to improve soil fertility or as forage during the dry season for improving milk production. Since nitrogen (N) is considered the most limiting nutrient for agricultural production in the target area, the objective of this study was to quantify the soil surface N budgets at plot level in farmers fields over two cropping years for the traditional maize/bean rotation and the alternative maize/canavalia rotation. Mineral fertilizer N, seed N and symbiotically fixed N were summed up as N input to the system. Symbiotic N2 fixation was assessed using the 15N natural abundance method. Nitrogen output was quantified as N export via harvested products. Canavalia derived in average 69% of its N from the atmosphere. The amount of N fixed per hectare varied highly according to the biomass production, which ranged from 0 to 5,700kgha−1. When used as green manure, canavalia increased the N balance of the maize/canavalia rotation but had no effect on the N uptake of the following maize crop. When used as forage, it bears the risk of a soil N depletion up to 41kgNha−1 unless N would be recycled to the plot by animal manure. Without N mineral fertilizer application, the N budget remains negative even if canavalia was used as green manure. Therefore, the replenishment of soil N stocks by using canavalia may need a few years, during which the application of mineral N fertilizer needs to be maintained to sustain agricultural productio

Population Pharmacokinetics of Cabotegravir Following Oral Administration and Long‐Acting Intramuscular Injection in Real‐World People with HIV

Long‐acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real‐world reference percentile curves of cabotegravir concentrations, accounting for patient‐related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one‐compartment model with distinct first order‐absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady‐state of 8 months and an elimination half‐life of 4.6 weeks for long‐acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model‐based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4‐fold protein‐adjusted 90% inhibitory target concentration

Self-reported neurocognitive complaints in the Swiss HIV Cohort Study: a viral genome-wide association study

People with HIV may report neurocognitive complaints, with or without associated neurocognitive impairment, varying between individuals and populations. While the HIV genome could play a major role, large systematic viral genome-wide screens to date are lacking. The Swiss HIV Cohort Study biannually enquires neurocognitive complaints. We quantified broad-sense heritability estimates using partial ‘pol’ sequences from the Swiss HIV Cohort Study resistance database and performed a viral near full-length genome-wide association study for the longitudinal area under the curve of neurocognitive complaints. We performed all analysis (i) restricted to HIV Subtype B and (ii) including all HIV subtypes. From 8547 people with HIV with neurocognitive complaints, we obtained 6966 partial ‘pol’ sequences and 2334 near full-length HIV sequences. Broad-sense heritability estimates for presence of memory loss complaints ranged between 1% and 17% (Subtype B restricted 1–22%) and increased with the stringency of the phylogenetic distance thresholds. The genome-wide association study revealed one amino acid (Env L641E), after adjusting for multiple testing, positively associated with memory loss complaints (P = 4.3 * 10−6). Other identified mutations, while insignificant after adjusting for multiple testing, were reported in other smaller studies (Tat T64N, Env *291S). We present the first HIV genome-wide association study analysis of neurocognitive complaints and report a first estimate for the heritability of neurocognitive complaints through HIV. Moreover, we could identify one mutation significantly associated with the presence of memory loss complaints. Our findings indicate that neurocognitive complaints are polygenetic and highlight advantages of a whole genome approach for pathogenicity determination

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success

Self-reported neurocognitive complaints in the Swiss HIV Cohort Study: a viral genome-wide association study.

People with HIV may report neurocognitive complaints, with or without associated neurocognitive impairment, varying between individuals and populations. While the HIV genome could play a major role, large systematic viral genome-wide screens to date are lacking. The Swiss HIV Cohort Study biannually enquires neurocognitive complaints. We quantified broad-sense heritability estimates using partial 'pol' sequences from the Swiss HIV Cohort Study resistance database and performed a viral near full-length genome-wide association study for the longitudinal area under the curve of neurocognitive complaints. We performed all analysis (i) restricted to HIV Subtype B and (ii) including all HIV subtypes. From 8547 people with HIV with neurocognitive complaints, we obtained 6966 partial 'pol' sequences and 2334 near full-length HIV sequences. Broad-sense heritability estimates for presence of memory loss complaints ranged between 1% and 17% (Subtype B restricted 1-22%) and increased with the stringency of the phylogenetic distance thresholds. The genome-wide association study revealed one amino acid (Env L641E), after adjusting for multiple testing, positively associated with memory loss complaints (P = 4.3 * 10-6). Other identified mutations, while insignificant after adjusting for multiple testing, were reported in other smaller studies (Tat T64N, Env *291S). We present the first HIV genome-wide association study analysis of neurocognitive complaints and report a first estimate for the heritability of neurocognitive complaints through HIV. Moreover, we could identify one mutation significantly associated with the presence of memory loss complaints. Our findings indicate that neurocognitive complaints are polygenetic and highlight advantages of a whole genome approach for pathogenicity determination

Laurent inversion

There are well-understood methods, going back to Givental and Hori--Vafa, that to a Fano toric complete intersection X associate a Laurent polynomial f that corresponds to X under mirror symmetry. We describe a technique for inverting this process, constructing the toric complete intersection X directly from its Laurent polynomial mirror f. We use this technique to construct a new four-dimensional Fano manifold

A Population-Based Trachoma Prevalence Survey Covering Seven Districts of Sangha and Likouala Departments, Republic of the Congo.

PURPOSE: We set out to estimate the prevalence of trachoma and access to water and sanitation in seven suspected-trachoma-endemic districts of northern Congo, surveyed as a single evaluation unit. METHODS: From a complete list of rural villages in the seven districts, we systematically selected 22 with probability proportional to village size. In selected villages, we included all households where there were fewer than 25 in total, or used compact segment sampling to select a group of approximately 20 households by random draw. In each selected household, all consenting residents aged ≥1 year were examined by Global Trachoma Mapping Project-certified trachoma graders, and data collected on household-level access to water and sanitation. RESULTS: In November and December 2015, 466 households were visited in 22 villages, and 2081 (88%) of 2377 residents of those households were examined. No examined individual had trichiasis. The age-adjusted prevalence of the active trachoma sign trachomatous inflammation-follicular (TF) in 1-9-year-olds was 2.5% (95%CI 0.9-4.5%). Only 39% (95%CI 35-44%) of households had access to an improved source of drinking water. Only 10% (95%CI 7-13%) of households had access to an improved sanitation facility. CONCLUSION: Trachoma is not a public health problem in this part of Congo. Access to water and sanitation is inadequate

Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (Ciita) Expression

Cell surface expression of major histocompatibility complex class II (MHCII) molecules is increased during the maturation of dendritic cells (DCs). This enhances their ability to present antigen and activate naive CD4+ T cells. In contrast to increased cell surface MHCII expression, de novo biosynthesis of MHCII mRNA is turned off during DC maturation. We show here that this is due to a remarkably rapid reduction in the synthesis of class II transactivator (CIITA) mRNA and protein. This reduction in CIITA expression occurs in human monocyte-derived DCs and mouse bone marrow–derived DCs, and is triggered by a variety of different maturation stimuli, including lipopolysaccharide, tumor necrosis factor α, CD40 ligand, interferon α, and infection with Salmonella typhimurium or Sendai virus. It is also observed in vivo in splenic DCs in acute myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalitis. The arrest in CIITA expression is the result of a transcriptional inactivation of the MHC2TA gene. This is mediated by a global repression mechanism implicating histone deacetylation over a large domain spanning the entire MHC2TA regulatory region

Deconstructive Aporias: Quasi-Transcendental and Normative

This paper argues that Derrida’s aporetic conclusions regarding moral and political concepts, from hospitality to democracy, can only be understood and accepted if the notion of différance and similar infrastructures are taken into account. This is because it is the infrastructures that expose and commit moral and political practices to a double and conflictual (thus aporetic) future: the conditional future that projects horizonal limits and conditions upon the relation to others, and the unconditional future without horizons of anticipation. The argument thus turns against two kinds of interpretation: the first accepts normative unconditionality in ethics but misses its support by the infrastructures. The second rejects unconditionality as a normative commitment precisely because the infrastructural support for unconditionality seems to rule out that it is normatively required. In conclusion, the article thus reconsiders the relation between a quasi-transcendental argument and its normative implications, suggesting that Derrida avoids the naturalistic fallacy