Accuracy of C-reactive protein and a differentiated white cell count in diagnosing tuberculosis.

Background: Tuberculosis (TB) is treatable with a high cure rate. In South Africa, 70% of pulmonary TB is microbiologically confirmed. Autopsy studies of HIV-positive people found 45.7% undiagnosed TB cases. Objectives: The primary objective investigated whether CRP and a differentiated white cell count (WCC) and ratios thereof are useful screening tools for TB. Method: This retrospective cross-sectional study included adult patients admitted to two tertiary hospitals in Bloemfontein with TB workups between April 2016 and September 2019. National Health Laboratory Service (NHLS) provided laboratory data. Tuberculosis Xpert® MTB/RIF, Xpert® MTB/RIF Ultra and TB culture were used as reference standard for TB diagnosis. Results: The study population comprised 1294 patients; 15.1% had TB, 56.0% were male and 63.1% HIV-positive. Patients with TB were younger (p < 0.0001; 95% CI: -8;-3 years). In the total population, WCC had the highest area under the curve (0.59). White cell count (p < 0.0001), neutrophils (p = 0.0003) and lymphocytes (p = 0.0394) were lower in TB patients, and CRP-WCC ratio (CWR) (p = 0.0009) and CRP-lymphocyte ratio (CLR) (p = 0.0386) higher. In HIV-positive patients, WCC (p = 0.0003), neutrophils (p = 0.002) and lymphocytes (p = 0.0491) were lower in TB patients and CWR (p = 0.0043) higher. No parameter reached the World Health Organization screening targets of 70% specificity with 90% sensitivity. Conclusion: Differentiated WCC and CRP are not useful in screening hospitalised patients for TB in our setting. Contribution: Our study guides future research to augment current screening and diagnostic algorithms for TB, specifically in advanced HIV disease.

Measurement of resonant bend loss in anti-resonant hollow core optical fiber: erratum.

An error on the part of the authors in drafting resulted in Eq. (3) being incorrect in the published paper [Opt. Express25, 20612 (2017)10.1364/OE.25.020612]. We present a corrected version of the equation. It should be noted that this does not affect the presented results or conclusions of the paper.

A microfluidic finger-actuated blood lysate preparation device enabled by rapid acoustofluidic mixing.

For many blood-based diagnostic tests, including prophylactic drug analysis and malaria assays, red blood cells must be lysed effectively prior to their use in an analytical workflow. We report on a finger-actuated blood lysate preparation device, which utilises a previously reported acoustofluidic micromixer module. The integrated device includes a range of innovations from a sample interface, to the integration of blisters on a laser engraved surface and a large volume (130 µL) one-stroke manual pump which could be useful in other low-cost microfluidic-based point-of-care devices. The adaptability of the acoustic mixer is demonstrated on highly viscous fluids, including whole blood, with up to 65% percent volume fraction of red blood cells. Used in conjunction with a lysis buffer, the micromixer unit is also shown to lyse a finger-prick (approximately 20 µL) blood sample in 30 seconds and benchmarked across ten donor samples. Finally, we demonstrate the ease of use of the fully integrated device. Cheap, modular, but reliable, finger-actuated microfluidic functions could open up opportunities for the development of diagnostics with minimal resources.

On the genetics of malaria parasites, a memoir: Part II, the diversity and phylogeny of the rodent malaria parasites.

In this abbreviated extract of his memoirs of a life in malaria research, Richard Carter (1945-2021) describes the expansion and genetic characterisation of the rodent malaria parasite collection in Edinburgh, culminating in the description of four species, Plasmodium yoelii, Plasmodium berghei, Plasmodium chabaudi and Plasmodium vinckei, and the separation of these into multiple sub-species. The origins of the use of P. chabaudi for the investigation of the genetic determinants of drug resistance in malaria parasites is discussed.

On the genetics of malaria parasites, a memoir: Part III, Genetic crossing in human malaria parasites.

In this abbreviated extract of his memoirs of a life in malaria research, Richard Carter (1945-2021) describes the history of the first genetic cross with the human malaria parasite, Plasmodium falciparum. This work followed on from Richard's initial involvement in the establishment of the field of malaria parasite genetics using the malaria parasites of rodents, the history of which is recounted in Parts I [1] and II [2] of this series. EDITORS' NOTE: This manuscript is an abridged excerpt from Richard Carter's first volume of memoirs describing his career in malaria research. Both volumes, the first concerning malaria parasite genetics, the second focussing on transmission and transmission blocking, are housed in the Wellcome Collection, London [3,4]. Electronic copies of the unabridged memoirs are available to the interested reader upon request to the Editors.

On the genetics of malaria parasites, a memoir: Part I, rodent malaria parasites and the first genetic crosses.

In this abbreviated extract of his memoirs of a life in malaria research, Richard Carter (1945-2021) describes the beginnings of malaria parasite genetics research at Edinburgh university, culminating in the first laboratory genetic cross between two strains of malaria parasites. EDITORS' NOTE: This manuscript is an abridged excerpt from Richard Carter's first volume of memoirs describing his career in malaria research. Both volumes, the first concerning malaria parasite genetics, the second focussing on transmission and transmission blocking, are housed in the Wellcome Collection, London [1,2]. Electronic copies of the unabridged memoirs are available to the interested reader upon request to the Editors. These memoirs began as a series of 'recollections' written to a PhD student in March 2014, and were expanded and revised by the author up to 2018. Apart from abridgement, the text is presented in its original form, preserving the informal style in which it was written.

Academia's responses to crisis: A bibliometric analysis of literature on online learning in higher education during COVID-19.

This paper aimed to provide a holistic view of research that investigated online learning in higher education around the globe during COVID-19 utilizing a bibliometric analysis. The researchers used co-citation analysis and text mining afforded by VOSviewer to document and analyze research patterns and topics reported in peer-reviewed documents published between January 2020 and August 2021. Findings of this study indicated that scholars from 103 countries or regions from the Global North and Global South investigated a wide array of topics, such as use of various technologies and strategies, redesigned curriculum, student perceptions and psychological impacts of the pandemic-imposed online learning. Many researchers applied technology acceptance theories and structural equation modeling to investigate factors associated with adoption and impacts of the pandemic-imposed online learning. Of the large quantity of research, medical education and chemical education were the most investigated disciplines. Inquiry-based learning, discovery learning, hands-on learning and collaborative learning emerged as instructional approaches frequently discussed or utilized across the target studies. This paper discussed (a) ongoing and emerging challenges to online higher education, (b) placing innovative pedagogies at the forefront of online learning, and (c) rapid, but imbalanced distribution of evolving literature based on the findings.

Picosecond laser microwelding of AlSi-YAG for laser system assembly.

We report the successful picosecond laser welding of AlSi and YAG. This material combination is of significant interest to the field of laser design and construction. Parameter maps are presented that demonstrate the impact of pulse energy and focal position on the resultant weld. Weld performance relevant to industrial applications is measured, i.e., shear strength, process yield, and absolute thermal resistance are presented.

The hyoid as a sound conducting apparatus in laryngeally echolocating bats.

The morphology of the stylohyal-tympanic bone articulation found in laryngeally echolocating bats is highly indicative of a function associated with signal production. One untested hypothesis is that this morphology allows the transfer of a sound signal from the larynx to the tympanic bones (auditory bulla) via the hyoid apparatus during signal production by the larynx. We used µCT data and finite element analysis to model the propagation of sound through the hyoid chain into the tympanic bones to test this hypothesis. We modeled sound pressure (dB) wave propagation from the basihyal to the tympanic bones, vibratory behavior (m) of the stylohyal-tympanic bone unit, and the stylohyal and tympanic bones when the stylohyal bone is allowed to pivot on the tympanic bone. Sound pressure wave propagation was modeled using the harmonic acoustics solver in ANSYS and vibratory behavior was modeled using coupled modal and harmonic response analyses in ANSYS. For both analyses (harmonic acoustics and harmonic response), the input excitation on the basihyal and thyrohyals was modeled as the estimated pressure (Pa) imposed by the collision of the vibrating thyroid cartilage of the larynx against these bones during signal production. Our models support the hypothesis that this stereotypical hyoid morphology found in laryngeally echolocating bats can transfer sound to the auditory bullae at an amplitude that is likely heard for the species Artibeus jamaicensis and Rhinolophus pusillus.

The role of improved housing and living environments in malaria control and elimination.

Malaria risk and endemicity is often associated with the nature of human habitation and living environment. The disappearance of malaria from regions where it had been endemic for centuries, such as coastal areas of southern England, has been attributed, at least in part, to improvement in the quality of housing. Moreover, indigenous malaria transmission ceased throughout England without the necessity to eliminate the vector mosquitoes. The principles of malaria transmission, as formulated following the thinking of the pioneers of malaria epidemiology, Ronald Ross and George Macdonald, show how this may happen. Malaria ceases to be sustainable where its reproduction number, R0, the number of new cases generated on average for each existing case of malaria, falls below 1. In the terms of a Ross/Macdonald analysis the reduced contact between humans and blood-feeding mosquitoes that is achieved through housing that is secure against mosquito entry can have a powerful effect in reducing malaria R0. The island of Sri Lanka, where malaria had been endemic probably for centuries previously, has reported no indigenous cases of malaria since 2012. The disappearance of malaria from Sri Lanka followed an effective attack upon malaria transmission by the Sri Lanka Anti Malaria Campaign. The targeted and enhanced efforts of this campaign launched in 1999, drove the malaria R0 below 1 for most of the period up to 2012, leading to a nearly continuous decline in malaria cases until their extinction. The decades leading up to the launch of these efforts were ones of general improvement of living environment and notably in the quality of housing stock. Studies in the late 1980s had shown that quality of housing in a highly malarious district of Sri Lanka was a strong determinant of malaria risk. Through its effects on malaria R0, improved housing is likely to have facilitated the malaria control and cessation of indigenous malaria transmission in Sri Lanka and that it will help reduce the risk of the re-introduction of malaria to the island.

Impact of nonlinear effects on transmission losses of hollow-core antiresonant negative curvature optical fiber.

We investigate the impact of input pulse duration and peak power of a femtosecond laser on pulse broadening and propagation losses in selected hollow-core antiresonant fiber (HC-ARF). The mixed effects of strong self-phase modulation and relatively weak Raman scattering broaden the spectral width, which in turn causes a portion of the output spectrum to exceed the transmission band of the fiber, resulting in transmission losses. By designing and setting up a gas flow control system and a vacuum system, the nonlinear behavior of the fiber filled with different pressurized gases is investigated. The experimental results show that replacing the air molecules in the fiber core with argon can weaken pulse broadening and increase the transmittable peak power by 14 MW for a given 122 MW input, while a vacuum system can reduce the nonlinearity to a larger extent, therefore enhancing the transmission of HC-ARF by at least 26 MW.

Reinforcement of the larynx and trachea in echolocating and non-echolocating bats.

The synchronization of flight mechanics with respiration and echolocation call emission by bats, while economizing these behaviors, presumably puts compressive loads on the cartilaginous rings that hold open the respiratory tract. Previous work has shown that during postnatal development of Artibeus jamaicensis (Phyllostomidae), the onset of adult echolocation call emission rate coincides with calcification of the larynx, and the development of flight coincides with tracheal ring calcification. In the present study, I assessed the level of reinforcement of the respiratory system in 13 bat species representing six families that use stereotypical modes of echolocation (i.e. duty cycle % and intensity). Using computed tomography, the degree of mineralization or ossification of the tracheal rings, cricoid, thyroid and arytenoid cartilages were determined for non-echolocators, tongue clicking, low-duty cycle low-intensity, low-duty cycle high-intensity, and high-duty cycle high-intensity echolocating bats. While all bats had evidence of cervical tracheal ring mineralization, about half the species had evidence of thoracic tracheal ring calcification. Larger bats (Phyllostomus hastatus and Pterpodidae sp.) exhibited more extensive tracheal ring mineralization, suggesting an underlying cause independent of laryngeal echolocation. Within most of the laryngeally echolocating species, the degree of mineralization or ossification of the larynx was dependent on the mode of echolocation system used. Low-duty cycle low-intensity bats had extensively mineralized cricoids, and zero to very minor mineralization of the thyroids and arytenoids. Low-duty cycle high-intensity bats had extensively mineralized cricoids, and patches of thyroid and arytenoid mineralization. The high-duty cycle high-intensity rhinolophids and hipposiderid had extensively ossified cricoids, large patches of ossification on the thyroids, and heavily ossified arytenoids. The high-duty cycle high-intensity echolocator, Pteronotus parnellii, had mineralization patterns and laryngeal morphology very similar to the other low-duty cycle high-intensity mormoopid species, perhaps suggesting relatively recent evolution of high-duty cycle echolocation in P. parnellii compared with the Old World high-duty cycle echolocators (Rhinolophidae and Hipposideridae). All laryngeal echolocators exhibited mineralized or ossified lateral expansions of the cricoid for articulation with the inferior horn of the thyroid, these were most prominent in the high-duty cycle high-intensity rhinolophids and hipposiderid, and least prominent in the low-duty cycle low-intensity echolocators. The non-laryngeal echolocators had extensively ossified cricoid and thyroid cartilages, and no evidence of mineralization/ossification of the arytenoids or lateral expansions of the cricoid. While the non-echolocators had extensive ossification of the larynx, it was inconsistent with that seen in the laryngeal echolocators.

The value of monitoring data in a process evaluation of hygiene behaviour change in Community Health Clubs to explain findings from a cluster-randomised controlled trial in Rwanda.

BACKGROUND: A cluster-Randomised Controlled Trial evaluation of the impact of the Community Health Clubs (CHCs) in the Community Based Environmental Health Promotion Programme in Rwanda in 2015 appeared to find little uptake of 7 hygiene indicators 1 year after the end of the intervention, and low impact on prevention of diarrhoea and stunting. METHODS: Monitoring data was revisited through detailed community records with all the expected inputs, outputs and external determinants analysed for fidelity to the research protocol. Five household inventory observations were taken over a 40-month period including 2 years after the end of the cRCT in a random selection of the 50 intervention CHCs and data compared to that of the trial. Focus Group Discussion with all Environmental Health Officers of the Ministry of Health provided context to understand the long-term community dynamics of hygiene behaviour change. RESULTS: It was found that the intervention had been jeopardised by external determinants with only 54% fidelity to protocol. By the end of the designated intervention period in June 2014, the treatment had reached only 58% of households with 41% average attendance at training sessions by the 4056 registered members and 51% mean completion rate of 20+ sessions. Therefore only 10% of 50 CHCs provided the full so-called 'Classic' training as per-protocol. However, sustainability of the CHCs was high, with all 50 being active 2 years after the end of the cRCT and over 80% uptake of recommended practices of the same 7 key indicators as the trial was achieved by 2017. CONCLUSIONS: The cRCT conclusion that the case study of Rusizi District does not encourage the use of the CHC model for scaling up, raises concerns over the possible misrepresentation of the potential of the holistic CHC model to achieve health impact in a more realistic time frame. It also questions the appropriateness of apparently rigorous quantitative research, such as the cluster-Randomised Controlled Trial as conducted in Rusizi District, to adequately assess community dynamics in complex interventions.

A specific proteinase 3 activity footprint in α1-antitrypsin deficiency.

α1-Antitrypsin (α1-AT) deficiency is a risk factor for emphysema due to tissue damage by serine proteases. Neutrophil elastase (NE) has long been considered the enzyme responsible. However, proteinase 3 (PR3) also produces the pathological features of chronic obstructive pulmonary disease (COPD), is present in the same granules in the neutrophil and is inhibited after NE. We developed a specific footprint assay for PR3 activity and assessed its relationship to an NE footprint in α1-AT deficiency. An ELISA was developed for the specific PR3 fibrinogen cleavage site Aα-Val541. Levels were measured in plasma from 239 PiZZ patients, 94 PiSZ patients, 53 nondeficient healthy smokers and 78 individuals with usual COPD. Subjects underwent extensive demographic characterisation including full lung function and lung computed tomography scanning. Aα-Val541 was greater than the NE footprint in all cohorts, consistent with differential activity. Values were highest in the PiZZ α1-AT-deficient patients and correlated with the NE marker Aα-Val360, but were ∼17 times higher than for the NE footprint, consistent with a greater potential contribution to lung damage. Aα-Val541 was related cross-sectionally to the severity of lung disease (forced expiratory volume in 1 s % pred: rs= -0.284; p<0.001) and was sensitive to augmentation therapy, falling from 287.2 to 48.6 nM (p<0.001). An in vivo plasma footprint of PR3 activity is present in greater quantities than an NE footprint in patients with α1-AT deficiency, is sensitive to augmentation therapy and represents a likely biomarker for dose-ranging studies.

Using Hamiltonian Monte Carlo to estimate the log-linear cognitive diagnosis model via Stan.

The Bayesian literature has shown that the Hamiltonian Monte Carlo (HMC) algorithm is powerful and efficient for statistical model estimation, especially for complicated models. Stan, a software program built upon HMC, has been introduced as a means of psychometric modeling estimation. However, there are no systemic guidelines for implementing Stan with the log-linear cognitive diagnosis model (LCDM), which is the saturated version of many cognitive diagnostic model (CDM) variants. This article bridges the gap between Stan application and Bayesian LCDM estimation: Both the modeling procedures and Stan code are demonstrated in detail, such that this strategy can be extended to other CDMs straightforwardly.

Rapid Laser Manufacturing of Microfluidic Devices from Glass Substrates.

Conventional manufacturing of microfluidic devices from glass substrates is a complex, multi-step process that involves different fabrication techniques and tools. Hence, it is time-consuming and expensive, in particular for the prototyping of microfluidic devices in low quantities. This article describes a laser-based process that enables the rapid manufacturing of enclosed micro-structures by laser micromachining and microwelding of two 1.1-mm-thick borosilicate glass plates. The fabrication process was carried out only with a picosecond laser (Trumpf TruMicro 5×50) that was used for: (a) the generation of microfluidic patterns on glass, (b) the drilling of inlet/outlet ports into the material, and (c) the bonding of two glass plates together in order to enclose the laser-generated microstructures. Using this manufacturing approach, a fully-functional microfluidic device can be fabricated in less than two hours. Initial fluid flow experiments proved that the laser-generated microstructures are completely sealed; thus, they show a potential use in many industrial and scientific areas. This includes geological and petroleum engineering research, where such microfluidic devices can be used to investigate single-phase and multi-phase flow of various fluids (such as brine, oil, and CO2) in porous media.

Worldwide Engagement for Digitizing Biocollections (WeDigBio): The Biocollections Community's Citizen-Science Space on the Calendar.

The digitization of biocollections is a critical task with direct implications for the global community who use the data for research and education. Recent innovations to involve citizen scientists in digitization increase awareness of the value of biodiversity specimens; advance science, technology, engineering, and math literacy; and build sustainability for digitization. In support of these activities, we launched the first global citizen-science event focused on the digitization of biodiversity specimens: Worldwide Engagement for Digitizing Biocollections (WeDigBio). During the inaugural 2015 event, 21 sites hosted events where citizen scientists transcribed specimen labels via online platforms (DigiVol, Les Herbonautes, Notes from Nature, the Smithsonian Institution's Transcription Center, and Symbiota). Many citizen scientists also contributed off-site. In total, thousands of citizen scientists around the world completed over 50,000 transcription tasks. Here, we present the process of organizing an international citizen-science event, an analysis of the event's effectiveness, and future directions-content now foundational to the growing WeDigBio event.