Insights from quantitative and mathematical modelling on the proposed 2030 goal for gambiense human African trypanosomiasis (gHAT)

Gambiense human African trypanosomiasis (gHAT) is a parasitic, vector-borne neglected tropical disease that has historically affected populations across West and Central Africa and can result in death if untreated. Following from the success of recent intervention programmes against gHAT, the World Health Organization (WHO) has defined a 2030 goal of global elimination of transmission (EOT). The key proposed indicator to measure achievement of the goal is to have zero reported cases. Results of previous mathematical modelling and quantitative analyses are brought together to explore both the implications of the proposed indicator and the feasibility of achieving the WHO goal. Whilst the indicator of zero case reporting is clear and measurable, it is an imperfect proxy for EOT and could arise either before or after EOT is achieved. Lagging reporting of infection and imperfect diagnostic specificity could result in case reporting after EOT, whereas the converse could be true due to underreporting, lack of coverage, and cryptic human and animal reservoirs. At the village-scale, the WHO recommendation of continuing active screening until there are three years of zero cases yields a high probability of local EOT, but extrapolating this result to larger spatial scales is complex. Predictive modelling of gHAT has consistently found that EOT by 2030 is unlikely across key endemic regions if current medical-only strategies are not bolstered by improved coverage, reduced time to detection and/or complementary vector control. Unfortunately, projected costs for strategies expected to meet EOT are high in the short term and strategies that are cost-effective in reducing burden are unlikely to result in EOT by 2030. Future modelling work should aim to provide predictions while taking into account uncertainties in stochastic dynamics and infection reservoirs, as well as assessment of multiple spatial scales, reactive strategies, and measurable proxies of EOT

Smanjeni omjer mineralnog ulja poboljšava prinos blastocista u sustavu mikrojažica i jednozametnim kulturama u poliesterskim mrežama - kratko priopćenje.

It is common to apply a mineral oil (MO) overlay to in vitro embryo cultures, even though the use of MO may be harmful to embryo development. To examine whether the volume of MO used in overlays for well-of-the-well (WOW) and polyester mesh (PM) single-embryo culture systems can be reduced, two sets of experiments were performed and the resulting blastocyst formation rates were compared with a conventional group (CG) embryo culture system. In Experiment 1, groups of 20 embryos in 100 μL microdrops of CDM-2 medium were plated in Petri dishes and then were covered with 3.5 mL of MO (resulting in a 1:35 ratio of medium to MO). Groups of 20 embryos were also placed in four-well plates in 400 μL CDM-2 medium per well, and the wells were covered with 400 μL MO (resulting in a 1:1 ratio of medium to MO). In Experiment 2, groups of 20 embryos were plated in four-well plates with 400 μL CDM-2 medium per well, and 1 mL of purified water was added to the center hole of the plate. Two sets of these plates were set up in parallel, and only one of the plates received an additional 400 μL of MO per well (resulting in a 1:1 ratio of medium to MO). A greater percentage of embryos reached the blastocyst stage when they were cultured in a 1:1 ratio of medium to MO, compared with embryos that were cultured in a 1:35 ratio of medium to MO (55 % vs. 41 %, respectively; P<0.01). In addition, a greater percentage of embryos reached the blastocyst stage in the WOW and PM systems that included a 1:1 ratio of medium to MO overlay than the embryos that were cultured in the presence of water in the central hole of a four-well plate without MO (48 % vs. 39 %, respectively; P<0.01). Therefore, a 1:1 ratio of medium to MO was found to improve blastocyst rates in both WOW and PM embryo culture systems.U in vitro kulturama zametaka uobičajeno je primjenjivati sloj mineralnog ulja (MU), iako to može biti štetno za razvoj embrija. U radu su provedeni pokusi s ciljem da se istraži može li se smanjiti količina primijenjenog MU u sustavu mikrojažica i u poliesterskim mrežama za uzgoj pojedinačnog zametka. Pri tome je stopa nastalih blastocista bila uspoređena s konvencionalnim načinom uzgoja zametaka. U prvom pokusu su skupine od 20 zametaka u mikrokapi od 100 μL CDM-2 medija bile stavljene na podlogu u Petrijeve zdjelice i nakon toga prekrivene s 3,5 mL MU (omjer između medija i MU iznosio je 1:35). Skupine od 20 zametaka također su bile smještene u četverodijelne plitice s 400 μL CDM-2 medija po jažici i prekrivene s 400 μL MU (omjer između medija i MU iznosio je 1:1). U drugom pokusu, skupine od 20 zametaka bile su smještene u četverodijelne plitice s 400 μL CDM-2 medija po jažici, u čiji je središnji otvor dodan 1 mL pročišćene vode. Dvije skupine tih plitica bile su istodobno postavljene, a samo u jednu pliticu dodano je 400 μL MU po jažici (omjer između medija i MU iznosio je 1:1). Veći postotak embrija dosegao je stadij blastociste kada je u kulturi bio primijenjen omjer 1:1 između medija i MU. U usporedbi sa zametcima kod kojih je u kulturi bio primijenjen omjer između medija i MU 1:35, razlika je iznosila 55 % prema 41 %, P<0,01. Osim toga, veći postotak zametaka dosegnuo je stadij blastociste u sustavu mikrojažica i poliesterskih mrežica u kojima je omjer između medija i MU bio 1:1, nego što je to bio slučaj kad je kulturi zametaka u središnjoj jažici plitice bila dodana voda (48 % prema 39 %, P<0,01). Utvrđeno je da omjer 1:1 između medija i MU poboljšava stopu razvijenih blastocista u oba sustava

Finite size scaling for quantum criticality using the finite-element method

Finite size scaling for the Schr\"{o}dinger equation is a systematic approach to calculate the quantum critical parameters for a given Hamiltonian. This approach has been shown to give very accurate results for critical parameters by using a systematic expansion with global basis-type functions. Recently, the finite element method was shown to be a powerful numerical method for ab initio electronic structure calculations with a variable real-space resolution. In this work, we demonstrate how to obtain quantum critical parameters by combining the finite element method (FEM) with finite size scaling (FSS) using different ab initio approximations and exact formulations. The critical parameters could be atomic nuclear charges, internuclear distances, electron density, disorder, lattice structure, and external fields for stability of atomic, molecular systems and quantum phase transitions of extended systems. To illustrate the effectiveness of this approach we provide detailed calculations of applying FEM to approximate solutions for the two-electron atom with varying nuclear charge; these include Hartree-Fock, density functional theory under the local density approximation, and an "exact"' formulation using FEM. We then use the FSS approach to determine its critical nuclear charge for stability; here, the size of the system is related to the number of elements used in the calculations. Results prove to be in good agreement with previous Slater-basis set calculations and demonstrate that it is possible to combine finite size scaling with the finite-element method by using ab initio calculations to obtain quantum critical parameters. The combined approach provides a promising first-principles approach to describe quantum phase transitions for materials and extended systems.Comment: 15 pages, 19 figures, revision based on suggestions by referee, accepted in Phys. Rev.

The Relationship Between Blood Sample Volume and Diagnostic Sensitivity of Blood Culture for Typhoid and Paratyphoid Fever: A Systematic Review and Meta-Analysis.

BACKGROUND: Blood culture is the standard diagnostic method for typhoid and paratyphoid (enteric) fever in surveillance studies and clinical trials, but sensitivity is widely acknowledged to be suboptimal. We conducted a systematic review and meta-analysis to examine sources of heterogeneity across studies and quantified the effect of blood volume. METHODS: We searched the literature to identify all studies that performed blood culture alongside bone marrow culture (a gold standard) to detect cases of enteric fever. We performed a meta-regression analysis to quantify the relationship between blood sample volume and diagnostic sensitivity. Furthermore, we evaluated the impact of patient age, antimicrobial use, and symptom duration on sensitivity. RESULTS: We estimated blood culture diagnostic sensitivity was 0.59 (95% confidence interval [CI], 0.54-0.64) with significant between-study heterogeneity (I2, 76% [95% CI, 68%-82%]; P < .01). Sensitivity ranged from 0.51 (95% CI, 0.44-0.57) for a 2-mL blood specimen to 0.65 (95% CI, 0.58-0.70) for a 10-mL blood specimen, indicative of a relationship between specimen volume and sensitivity. Subgroup analysis showed significant heterogeneity by patient age and a weak trend towards higher sensitivity among more recent studies. Sensitivity was 34% lower (95% CI, 4%-54%) among patients with prior antimicrobial use and 31% lower after the first week of symptoms (95% CI, 19%-41%). There was no evidence of confounding by patient age, antimicrobial use, symptom duration, or study date on the relationship between specimen volume and sensitivity. CONCLUSIONS: The relationship between the blood sample volume and culture sensitivity should be accounted for in incidence and next-generation diagnostic studies

Nonadiabatic Dynamics of Atoms in Nonuniform Magnetic Fields

Dynamics of neutral atoms in nonuniform magnetic fields, typical of quadrupole magnetic traps, is considered by applying an accurate method for solving nonlinear systems of differential equations. This method is more general than the adiabatic approximation and, thus, permits to check the limits of the latter and also to analyze nonadiabatic regimes of motion. An unusual nonadiabatic regime is found when atoms are confined from one side of the z-axis but are not confined from another side. The lifetime of atoms in a trap in this semi-confining regime can be sufficiently long for accomplishing experiments with a cloud of such atoms. At low temperature, the cloud is ellipsoidal being stretched in the axial direction and moving along the z-axis. The possibility of employing the semi-confining regime for studying the relative motion of one component through another, in a binary mixture of gases is discussed.Comment: 1 file, 17 pages, RevTex, 2 table

Impact of PEWS on Perceived Quality of Care During Deterioration in Children With Cancer Hospitalized in Different Resource-Settings

BackgroundChildren with cancer are at high risk for clinical deterioration and subsequent mortality. Pediatric Early Warning Systems (PEWS) have proven to reduce the frequency of clinical deterioration in hospitalized patients. This qualitative study evaluates provider perspectives on the impact of PEWS on quality of care during deterioration events in a high-resource and a resource-limited setting.MethodsWe conducted semi-structured interviews with 83 healthcare staff (nurses, pediatricians, oncology fellows, and intensivists) involved in recent deterioration events at two pediatric oncology hospitals of different resource levels: St. Jude Children’s Research Hospital (SJCRH; n = 42) and Unidad Nacional de Oncología Pediátrica (UNOP; n = 41). Interviews were conducted in the participant’s native language (English or Spanish), translated into English, and transcribed. Transcripts were coded and analyzed inductively.ResultsProviders discussed both positive and negative perspectives of clinical deterioration events. Content analysis revealed “teamwork,” “experience with deterioration,” “early awareness,” and “effective communication” as themes associated with positive perception of events, which contributed to patient safety. Negative themes included “lack of communication,” “inexperience with deterioration,” “challenges with technology”, “limited material resources,” “false positive score,” and “objective tool.” Participants representing all disciplines across both institutions shared similar positive opinions. Negative opinions, however, differed between the two institutions, with providers at UNOP highlighting limited resources while those at SJCRH expressing concerns about technology misuse.ConclusionProviders that care for children with cancer find PEWS valuable to improve the quality of hospital care, regardless of hospital resource-level. Identified challenges, including inadequate critical care resources and challenges with technology, differ by hospital resource-level. These findings build on growing data demonstrating the positive impact of PEWS on quality of care and encourage wide dissemination of PEWS in clinical practice

Update of transmission modelling and projections of gambiense human African trypanosomiasis in the Mandoul focus, Chad

In recent years, a programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections led to a rapid decline in cases in the Mandoul focus of Chad. To represent the biology of transmission between humans and tsetse, we previously developed a mechanistic transmission model, fitted to data between 2000 and 2013 which suggested that transmission was interrupted by 2015. The present study outlines refinements to the model to: (1) Assess whether elimination of transmission has already been achieved despite low-level case reporting; (2) quantify the role of intensified interventions in transmission reduction; and (3) predict the trajectory of gHAT in Mandoul for the next decade under different strategies. Method Our previous gHAT transmission model for Mandoul was updated using human case data (2000–2019) and a series of model refinements. These include how diagnostic specificity is incorporated into the model and improvements to the fitting method (increased variance in observed case reporting and how underreporting and improvements to passive screening are captured). A side-by-side comparison of fitting to case data was performed between the models. Results We estimated that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (95% credible interval (CI) 99.9–100%, Specificity = 99.9%), the high screening and low infection levels mean that some recently reported cases with no parasitological confirmation might be false positives. We also find that the focus-wide tsetse reduction estimated through model fitting (95% CI 96.1–99.6%, Reduction = 99.1%) is comparable to the reduction previously measured by the decline in tsetse catches from monitoring traps. In line with previous results, the model suggests that transmission was interrupted in 2015 due to intensified interventions. Conclusions We recommend that additional confirmatory testing is performed in Mandoul to ensure the endgame can be carefully monitored. More specific measurement of cases, would better inform when it is safe to stop active screening and vector control, provided there is a strong passive surveillance system in place

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented