bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Causes of Death Identified Using Automated Verbal Autopsy and Complete Autopsy among Brought-in-Dead Cases at a Tertiary Hospital in Sub-Sahara Africa
Authors: Yokobori Yuta , Matsuura Jun , Sugiura Yasuo , Mutemba Charles , Julius Peter , Himwaze Cordelia , Nyahoda Martin , Mwango Chomba , Kazhumbula Lloyd , Yuasa Motoyuki , Munkombwe Brian , Mucheleng'anga Luchenga
Published: June 2022

Background Over one-third of deaths recorded at health facilities in Zambia are brought in dead (BID) and the causes of death (CODs) are not fully analyzed. The use of automated verbal autopsy (VA) has reportedly determined the CODs of more BID cases than the death notification form issued by the hospital. However, the validity of automated VA is yet to be fully investigated.

Objectives To compare the CODs identified by automated VA with those by complete autopsy to examine the validity of a VA tool.

Methods The study site was the tertiary hospital in the capital city of Zambia. From September 2019 to January 2020, all BID cases aged 13 years and older brought to the hospital during the daytime on weekdays were enrolled in this study. External COD cases were excluded. The deceased's relatives were interviewed using the 2016 World Health Organization VA questionnaire. The data were analyzed using InterVA, an automated VA tool, to determine the CODs, which were compared with the results of complete autopsies.

Results A total of 63 cases were included. The CODs of 50 BID cases were determined by both InterVA and complete autopsies. The positive predictive value of InterVA was 22%. InterVA determined the CODs correctly in 100% cases of maternal CODs, 27.5% cases of noncommunicable disease CODs, and 5.3% cases of communicable disease CODs. Using the three broader disease groups, 56.0% cases were classified in the same groups by both methods.

Conclusion While the positive predictive value was low, more than half of the cases were categorized into the same broader categories. However, there are several limitations in this study, including small sample size. More research is required to investigate the factors leading to discrepancies between the CODs determined by both methods to optimize the use of automated VA in Zambia.
Implementation of a Bedside Point-of-Care Ultrasound Program in a Large Academic Neonatal Intensive Care Unit
Authors: Pai Vidya V. , Noh Caroline Y. , Dasani Reedhi , Vallandingham Shelby , Manipon Christine , Haileselassie Bereketeab , Profit Jochen , Balasundaram Malathi , Davis Alexis S. , Bhombal Shazia
Published: June 2022

Objectives In the adult and pediatric critical care population, point-of-care ultrasound (POCUS) can aid in diagnosis, patient management, and procedural accuracy. For neonatal providers, training in ultrasound and the use of ultrasound for diagnosis and management is increasing, but use in the neonatal intensive care unit (NICU) is still uncommon compared with other critical care fields. Our objective was to describe the process of implementing a POCUS program in a large academic NICU and evaluate the role of ultrasound in neonatal care during early adaption of this program.

Study Design A POCUS program established in December 2018 included regular bedside scanning, educational sessions, and quality assurance, in collaboration with members of the cardiology, radiology, and pediatric critical care divisions. Core applications were determined, and protocols outlined guidelines for image acquisition. An online database included images and descriptive logs for each ultrasound.

Results A total of 508 bedside ultrasounds (76.8% diagnostic and 23.2% procedural) were performed by 23 providers from December 2018 to December 2020 in five core diagnostic applications: umbilical line visualization, cardiac, lung, abdomen (including bladder), and cranial as well as procedural applications. POCUS guided therapy and influenced clinical management in all applications: umbilical line assessment (26%), cardiac (33%), lung (14%), abdomen (53%), and cranial (43%). With regard to procedural ultrasound, 74% of ultrasound-guided arterial access and 89% of ultrasound-guided lumbar punctures were successful.

Conclusions Implementation of a POCUS program is feasible in a large academic NICU and can benefit from a team approach. Establishing a program in any NICU requires didactic opportunities, a defined scope of practice, and imaging review with quality assurance. Bedside clinician performed ultrasound findings can provide valuable information in the NICU and impact clinical management.

Key Points
Individual and community-level factors associated with non-institutional delivery of women of childbearing-age in Nigeria
Authors: Xu Yan , Peng Michael Yao-Ping , Ahuru Rolle Remi , Anser Muhammad Khalid , Osabohien Romanus , Aziz Ayesha
Published: June 2022

Maternal health is a major concern in Africa especially due to high level of maternal mortality in the region. A significant cause of high mortality is the unavailability of health facilities and preference for home-based delivery often carried out by unskilled health attendants. Reports reveal that 69% of young women in Nigeria opt for home-based delivery in Nigeria and some of these mothers lose their lives as a result of childbirth complications that are not properly attended to. This trend calls for urgent concern in the nation’s health system. Against this backdrop, this study examined the determinants of non-institutional delivery among women of reproductive age in Nigeria using the country’s National Demographic Health Survey [NDHS] (2018. Demographic health survey data. NPC and ICF, Abuja, Nigeria and Rockville. MD, USA) The data for this study include 12,567 of women of childbearing-age contained in the NDHS data. To analyse the data, the multilevel binary logistic regression was used to examine the determinants of non-institutional delivery among the women of childbearing-age. The results were presented using adjusted odds ratios (AOR) with 95% confidence interval. The result revealed that 56.8% of women preferred to have their children outside health institutions. The findings further revealed that educated women including urban dwellers, women with some level of formal education, high exposure to news media, high level of income and women with significant level of autonomy were less likely to deliver their babies outside health institutions. Based on the findings of the study, that there is the need to expand educational opportunities for Nigerian women, enhance and strengthen advocacy, and utilise focused group discussions, family outreach programmes and peer education to educate mothers on the benefits of using healthcare facilities during childbirth.
Gene and tissue atlases provide insights into nuclear mechanics
Authors: Thompson Avery
Published: June 2022

Co-occurrences with known mechanosensitive genes hint at further role of mechanical factors in gene expression.
Observation of non-thermal metastable ion velocity distributions in a miniaturized multi-dipole confined plasma device
Authors: Jiang Di , Yip Chi-Shung , Jin Chen-Yao , Zhang Wei , Wang Liang , Xu Guo-Sheng
Published: June 2022

Hot cathode discharges are common plasma sources for fundamental plasma physics studies and other applications due to their capability to produce quiescent plasma. This work presents experimental observations of presheath-associated non-thermal metastable ion velocity distributions in a miniaturized multi-dipole confined plasma device measured by laser-induced fluorescence. The intensity of this non-Maxwellian component is related to the collisions of these metastable ions with background particles. Additionally, the flow velocity of this component is lower than the Bohm velocity; thus, its energy is lower than the presheath potential drop kTe/2. This implies that these non-thermal metastable ion velocity distributions are formed via presheath acceleration and are associated with the source asymmetries of the miniaturized device. The strength decreases as the neutral pressure increases once the neutral pressure is adjusted, suggesting that the presheath length is the critical condition that determines whether these components can be observed.
Entropy stabilization of two-dimensional transition metal dichalcogenide alloys: A density functional theory study
Authors: Deshpande Aditya , Ratsch Christian , Ciobanu Cristian V. , Kodambaka Suneel
Published: June 2022

As high-entropy alloying provides an increasingly important avenue for widening the set of functional materials for a variety of applications, it is useful to uncover synthesis routes that do not rely on large temperatures for achieving entropic stabilization. Focusing on transition-metal dichalcogenides, we present direct computational evidence from density functional theory calculations that high-entropy disulfide (HES) alloys with five cations from groups 4–6 are thermodynamically stable at temperatures routinely achievable in conventional deposition systems. While all 126 sulfide combinations with five group 4–6 transition metals are thermodynamically favorable at low (<800 K) or medium (<1200 K) temperatures, we show that electronegativities, valence electron concentrations, and atomic radii of cations can help predict whether an HES alloy is stable in the 1-H or the 1-T structure. Furthermore, replacing one of the five cations with another, from outside groups 4–6, can still yield HES alloys with nearly planar layer morphologies and stabilization temperatures below 1200 K, albeit with some localized defects. These results demonstrate that a wide range of stable HES alloys can be synthesized experimentally as 2D layers, thereby providing facile ways for expanding the materials’ space with potential applications in electrochemical devices, catalysis, energy storage, or sensing.
Experimental investigation on the ignition dynamics of an annular combustor with multiple centrally staged swirling burners
Authors: Wang Hui , Zhong Liang , Barakat Elsayed , Xia Yifan , Tao Wenjie , Tong Xiaokang , Wang Gaofeng
Published: June 2022

The ignition behaviors of an annular combustor consisting of 16 centrally staged swirling burners are experimentally investigated in this work. This research is mainly focused on the light-round mechanism of burner-burner flame propagation. The swirling flow structure of the staged burner and the flow interaction between multiple burners in the annular combustor are well measured via the particle image velocimetry method. Two high speed cameras are applied to analyze the light-round process from the side view and the top view. The light-round time, ignition and extinction limits, flame propagating pattern, and dynamics of flame leading point are analyzed. Increasing the equivalence ratio, the light-round time decreases gradually. A more complicated “sawtooth” pattern of flame propagation is discovered during the burner to burner flame propagation, compared to that with non-staged burners. The trajectories of the flame leading points are moving in a “zigzag” pattern during the light-round process. The trajectories of the anti-clockwise leading point are near the inside wall, while the trajectories of the clockwise one are closer to the outside wall. For various equivalence ratios and airflow rates, the circumferential flame speeds of the clockwise flame front are constantly faster than the anti-clockwise one. In addition, the two flame speeds and their differences increase with larger equivalence ratio. These characteristics are very different from those in an annular combustor with non-staged burners.
Indirect physical mechanism of viscous forces: Vortex stretching and twisting
Authors: Lin L. M. , Wu Y. X.
Published: June 2022

In this paper, the indirect physical mechanism of viscous forces, i.e., vortex stretching and twisting, is theoretically explored. The local flow in the immediate neighborhood of a flat plate is analyzed. Only the viscous forces are considered. By introducing oppositely signed streamwise vorticity in such a region, the induced velocity and vorticity fields are obtained. Because the induced streamwise velocity varies along with both the wall-normal and spanwise directions, induced vertical and spanwise vorticities are generated. The induction sequence is first clarified. Then, two indirect effects of viscous forces are identified. The induced spanwise vorticity leads to the original two-dimensional spanwise vorticity increasing and decreasing alternately across the span, as the vortex stretching effect of viscous forces. The local spanwise vortex is distorted at positions where the streamwise vorticity is introduced, and the appearance of induced vertical vorticity at the same positions enhances this effect, as the vortex twisting effect of viscous forces.
The technique to symmetrize domain switching hysteresis loops in LiNbO3 domain-wall nanodevices with improved polarization retention
Authors: Zhuang Xiao , Wang Chao , Jiang An Quan
Published: June 2022

Ferroelectric devices have wide applications in nonvolatile random-access memories, sensors, actuators, and transducers. The built-in potential at the interfaces could result in poor polarization retention. Here, we found an effective way to independently adjust two coercive fields of LiNbO3 mesa-like domain wall devices in contact to two side electrodes at the surface. Taking advantage of the electrode shielding effect on the depolarization field across an interfacial layer, the near-zero coercive field increases almost linearly with respect to the extending length of one side electrode covering the tail of the reversed domain, enabling nonvolatile ferroelectric domain wall devices in good polarization retention and fast operation speeds.
Magneto-optical measurements of mesoscopic Nb superconducting structures using a ferromagnetic metal indicator layer
Authors: Heo Hyeokjun , Choi Won Beom , Ha Sangwook , Park Hangyeol , Jang Joonho
Published: June 2022

Imaging local magnetic fields produced by nano- and micrometer-scale superconductors has become a vital tool that can not only reveal crucial information on the vortex dynamics and order parameters of the superconducting materials but also visualize the working mechanism of superconducting devices made for quantum information. Here, we performed measurements of the magnetic field distributions of mesoscopic superconducting structures with various geometries by combining a thin ferromagnetic metal layer as a magneto-optical sensing element that responds to the environmental magnetic fields and a custom-made sensitive Sagnac interferometer. The sensitivity of the technique enables the observation of magnetic flux jumps due to individual vortex entries into nanostructured superconductors. In addition, with the control of incident power at a focused laser spot, we induce thermally driven movement of vortices that leaves a trace of a microscopic optical heating pattern.
Impact of molecular components on performance of multilayer graphene-based infrared emissivity modulator
Authors: Zhang Yufeng , Ke Haibo , Li Junxiao , Weng Zekai , Lin Tong , Peng Wenlian , Dai Mengyan , Mu Rui , Zhang Xue-Ao
Published: June 2022

Actively controlling the infrared emissivity of materials is critical for many applications, such as radiative cooling and thermal camouflage. Multilayer graphene (MLG) has shown great potential as a functional material with a tunable infrared emissivity. However, the spatial homogeneity in adjusting MLG's emissivity through ion intercalation is rather poor, which limits its practical applications. Here, we study how mixing various molecular components (e.g., ethanol) with ionic liquids affects the performance of MLG-based infrared emissivity modulators. The results indicate that introducing a moderate concentration of molecular components not only significantly improves spatial homogeneity in tuning emissivity but also enhances modulation depth, dynamic response, and the stability of the modulators. This is likely due to the increasing conductivity of the mixture and the improved wetting properties between the mixture and the separator, which leads to more effective charge transfer from ions in ionic liquids to carbons in graphene. The microscopic structure of MLG, revealed by Raman spectroscopy, confirms that the improvement in modulator performance is mostly due to homogeneous transportation of ions in the modulators. This not only sheds light on the underlying physics of the modulator but also greatly expands the options when selecting ionic liquids, thereby opening a new route for the modulator design.
Feasibility of using melatonin content in pepper (
Authors: Korkmaz Ahmet , Düver Elif , Szafrańska Katarzyna , Karaca Aygül , Köklü Ardıç Şebnem , Yakupoğlu Gökçen
Published: June 2022

The presence of melatonin, a known animal hormone, has been confirmed in many evolutionary distant organisms, including higher plants. It is known that melatonin increases tolerance to stress factors as a wide spectrum antioxidant. Tolerant genotypes have generally higher melatonin content than sensitive ones, and exposure to stressful conditions is known to increase endogenous melatonin levels. However, endogenous melatonin levels in seeds have never been used to select genotypes tolerant to abiotic stresses. Thus, in this study, the existence of possible relationship between seed melatonin levels of 28 pepper (Capsicum annuum L.) genotypes and their germination and emergence performance under chilling conditions (15°C) was investigated. The results indicated that these parameters were much better for pepper genotypes with higher seed melatonin contents while those having less than 2 ng g−1 additionally exhibited elevated levels of MDA and H2O2 but lower antioxidant enzyme activities. Thus, a positive relationship between seed melatonin content and chilling stress tolerance has been shown, suggesting a possible use of endogenous melatonin levels as a criterion in selecting chilling stress tolerant varieties. To save considerable time, money and labour, it is recommended that genotypes with lower melatonin contents are excluded from breeding programmes that aim to develop new stress tolerant genotypes.
An intrinsically stretchable and bendable electrochromic device
Authors: Lerond Michael , Raj A Mohan , Wu Veronica , Skene W G , Cicoira Fabio
Published: June 2022

Stretchable electrochromic devices (ECDs) were fabricated from electrospun PEDOT:PSS (poly(3, 4-ethylenedioxythiophene):polystyrene sulfonate) fibers. Stretchable and transparent electrodes with a sheet resistance of 1200 Ω sq−1 were prepared by depositing the conductive fibers on elastomeric substrates that were prepared from polydimethylsiloxane. The conductive substrates replaced the ITO coated glass electrodes that are typically used in ECDs. The functioning device was prepared from a flexible chitosan electrolytic gel and a 4, 7-bis(4-diphenylaminophenyl)−2, 1, 3-benzothiaziazole (TPA-BZT-TPA) electrochrome that were deposited on the streatchable transparent electrodes. The assembled device could be stretched to 150% its original length and bent to a curvature of 0.1. The device could be operated and switched between its yellow (off) and blue (on) states while being stretched and bent with a maximum contrast ΔT ≈ 30% at 805 nm and a coloration efficiency of 168 cm2 C−1. The stretchable device had an electrochromic contrast that was 30% greater than its counterpart that was prepared from conventional ITO-glass electrodes. The critical composition required for making devices truly stretchable was possible by evaluating the performance of five types of devices consisting of different layers.
Modulation of electrical and thermal transports through lattice distortion in BaTi1–x
Nb
x
O3 solid solutions
Authors: Zhang Yuqiao , Cho Hai Jun , Jiang Feng , Xia Chengliang , Chen Yue , Liu Weishu , Ohta Hiromichi
Published: June 2022

The electron and heat transports in solids are through the movement of carrier electrons and quantized lattice vibrations (phonons), which are sensitive to the lattice distortion and ionized impurities, and are essential aspects for the development of novel thermoelectric materials. In this study, we systematically investigated the modulations of electrical and thermal conductivities of BaTi1–x
Nb
x
O3 solid solution (BTNO, 0 ≤ x ≤ 1) epitaxial films. At room temperature, BaTiO3 belongs to tetragonal perovskite and exhibits electron conduction through doubly degenerated Ti 3d-t2g orbitals upon doping, while BaNbO3 belongs to cubic perovskite and exhibits metallic electron conduction through partially filled triply degenerate Nb 4d-t2g orbitals. By controlling the Ti/Nb ratio, we found a dual modulation effect on both the lattice structures and conduction band, which affects the electrical and thermal conductivities. Similar to the SrTi1–x
Nb
x
O3 solid solution (STNO, 0 ≤ x ≤ 1) system, a phase transition was detected at x ∼ 0.5, at which both the electron and heat transports exhibit abrupt changes. Unlike the transition in STNO, which was attributed to a polaronic phase transition, the transition in BTNO was due to contributions from both the lattice distortion and polaron effect. By controlling the lattice distortion, conduction band, and polaronic phase transitions, the electrical and thermal conductivity of BTNO epitaxial films are modulated within a much greater range than those of the STNO epitaxial films. Due to the double contribution of electron carriers and phonon to thermal conductivity (κ), the maximum κ modulation ratio of BTNO epitaxial films was ∼6.9. Our research provides an effective route to design electrical/thermal management materials.
Artificial atoms from cold bosons in one dimension
Authors: Brauneis Fabian , Backert Timothy G , Mistakidis Simeon I , Lemeshko Mikhail , Hammer Hans-Werner , Volosniev Artem G
Published: June 2022

We investigate the ground-state properties of weakly repulsive one-dimensional bosons in the presence of an attractive zero-range impurity potential. First, we derive mean-field solutions to the problem on a finite ring for the two asymptotic cases: (i) all bosons are bound to the impurity and (ii) all bosons are in a scattering state. Moreover, we derive the critical line that separates these regimes in the parameter space. In the thermodynamic limit, this critical line determines the maximum number of bosons that can be bound by the impurity potential, forming an artificial atom. Second, we validate the mean-field results using the flow equation approach and the multi-layer multi-configuration time-dependent Hartree method for atomic mixtures. While beyond-mean-field effects destroy long-range order in the Bose gas, the critical boson number is unaffected. Our findings are important for understanding such artificial atoms in low-density Bose gases with static and mobile impurities.
Stimulation of the tibial nerve—a randomised trial for urinary problems associated with Parkinson’s—the STARTUP trial
Authors: McClurg Doreen , Elders Andrew , Hagen Suzanne , Mason Helen , Booth Jo , Cunnington Anne-Louise , Walker Richard , Deane Katherine , Harari Danielle , Panicker Jalesh , Stratton Susan , McArthur Jaclyn , Sellers Ceri , Collins Marissa
Published: June 2022

Background

non-motor symptoms such as bladder dysfunction are common (80%) in people with Parkinson’s increasing the risk for falls with a negative impact on health-related costs and quality of life.

We undertook STARTUP to evaluate the clinical and cost-effectiveness of using an adhesive electrode to stimulate the transcutaneous tibial nerve stimulation (TTNS) to treat bladder dysfunction in people with Parkinson’s disease (PD).

Study design, materials and methods: STARTUP was a parallel two-arm, multi-centre, pragmatic, double-blind, randomised controlled trial. Each participant attended one clinic visit to complete consent, be randomised using a computer-generated system and to be shown how to use the device.

The trial had two co-primary outcome measures: International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the International Prostate Symptom Score (IPSS). These were completed at baseline, 6 and 12 weeks. A bladder frequency chart and resource questionnaire were also completed.

Results

two hundred forty two participants were randomised. About 59% of participants were male, the mean age was 69 years and mean time since diagnosis was 6 years. Questionnaire return rate was between 79 and 90%.

There was a statistically significantly lower score in the active group at 6 weeks in the IPSS questionnaire (mean difference (Standard deviation, SD) 12.5 (6.5) vs 10.9 (5.5), effect size −1.49, 95% CI −2.72, −0.25). There was no statistically significant change in any other outcome.

Conclusion

TTNS was demonstrated to be safe with a high level of compliance. There was a significant change in one of the co-primary outcome measures at the end of the treatment period (i.e. 6 weeks), which could indicate a benefit. Further fully powered RCTs are required to determine effective treatments.
1043 FRAGILITY FRACTURE RISK ASSESSMENT IN THE OLDER PERSON’S RAPID ACCESS CLINIC (OPRAC): A QUALITY IMPROVEMENT PROJECT
Authors: Dumenci O , Alhilani M , Malani S , Suh S
Published: June 2022

Background

One-in-two women and one-in-five men >50 years are expected to have an osteoporotic fracture during their lifetime. However, despite this 1-in-5 women who have broken a bone, break 3 or more before being diagnosed, highlighting the importance of early diagnosis.

Aim NICE recommends a fragility fracture risk assessment in all women aged >65 and men >75 years. However, during our review of patients attending OPRAC, we found that only 3% of patients had an assessment done. Therefore, the primary aim of this project was to improve risk assessment of fragility fractures in this setting.

Method

We analysed the data for patients attending OPRAC between 23.09.20–23.10.20 and 01.05.21–15.06.21. We captured 35 and 51 patients respectively and sought to identify what proportion of the population had an accurate height, weight and fragility fracture assessment. We carried out our QIP using the PDSA cycle. Our interventions consisted of departmental teaching, posters and inclusion of fracture risk assessment in our induction handbook.

Results

The risk assessment went up from 3% to 33% post-intervention and documentation of height and weight went up from 74% to 98%. We retrospectively calculated the FRAX score for every single patient to assess whether the patients were receiving the appropriate treatment according to their risk score. What was consistent across both cycles was that if a patient had a risk assessment done, they were far more likely to have the correct treatment—89% and 82% in cycles 1 and 2 vs. 54% and 30% in those who didn’t have an assessment.

Conclusion

The above highlights what we already know about the importance of early diagnosis and treatment of osteoporosis. The interventions we have implemented have made a difference however further incorporation of fragility fracture assessments in clinical protocols is needed to bring about sustained change.
1047 VALIDATION OF THE CHINESE VERSION OF THE KATZ INDEX OF INDEPENDENCE IN ACTIVITIES OF DAILY LIVING
Authors: Chui D L K , Yeung C K , Choi C W , Leung M N , Lui Y , Tam W Y , Tang K Y , Wong C , Wong Y , Yau C Y , Yeung T L , Lee J K L , Lee L Y K
Published: June 2022

Introduction

Among the instruments that measure an elder’s functional dependence level, the Katz Index of Independence in Activities of Daily Living has the advantages of being neutral, easy to use, valid, and reliable. It is a six-item instrument rating an elder’s functional dependence level in performing activities of daily living, including bathing, dressing, toileting, transferring, continence, and feeding. Each item can be rated nominally as 1 (does not require assistance to finish the activity) or 0 (requires assistance to finish the activity). By summing the score of the six items, the functional dependence level of an elder can be classified as independent (6 points), partially dependent (3–5 points), or dependent (< 2 points). The instrument has been translated from English to Chinese through forward and backward translation. This study aims to validate the Chinese version of the Katz Index of Independence in Activities of Daily Living (Katz ADL-Chinese).

Method

This was a validation study. The Katz ADL-Chinese was examined by an expert panel (one academic specialized on instrument validation, four academic specialized on translation, fifteen nurses specialized on geriatrics) for its semantic and content equivalence with the original English version. It was evaluated by another expert panel (one academic specialized on instrument validation and two nurses specialized on geriatrics) for its content validity. Moreover, it was tested and re-tested at 1-week interval on 30 Chinese-speaking elders in Hong Kong.

Results

Good result was achieved on the testing for semantic and content equivalence. All experts confirmed that the Katz ADL-Chinese was appropriately translated. Good content validity was observed. The context validity index at item-level and scale-level was 1.00, respectively. Good stability was observed as well. The test–retest reliability coefficient was 0.85.
1057 A CASE OF AUTOIMMUNE NECROTISING MYOSITIS
Authors: Phyoe A
Published: June 2022

Introduction

An 88-year-old previously independent lady presented with progressive proximal weakness of all limbs and multiple falls for 10 months. Her swallowing got difficult lately. She lost weight gradually in that duration but denied any other symptoms suggestive of malignancy. PMH—Hypothyroid, Mild cognitive impairment Drg History—Atorvastatin for years. Stopped in this admission.

On examination, she showed signs of proximal muscle weakness and areflexia in both upper and lower limbs without muscle tenderness. She had no facial nor eye muscle weakness. Sensory functions were intact. There were no rashes.

Investigations CK 2000 TSH 24 Inflammatory markers, white cell counts—non-significant Vitamin D—18 CT-Chest Abdomen Pelvis, CT-colonography—No evidence of malignancy Paraneoplastic antibodies—Negative Anti-OJ and anti-Ro52 Antibodies—positive ENA profile—negative Anti-RNP—equivocal HMG-CoA reductase antibodies (HMCR)—Positive.

Progress

Prednisolone was commenced and gradually increased to 60 mg once a day but there is no significant improvement clinically though creatinine kinase level had improved. She was unfortunately infected with COVID-19 infection in the stay which delayed the plan for muscle biopsy and EMG. It affected the plan for Intravenous Immunoglobulins and was later decided to be non-beneficial due to high risks of thromboembolic events and superimposed infections. Steroid was later switched to methotrexate. She was discharged to a rehab unit.

Conclusion

Necrotising Autoimmune Myopathy is a rare form of idiopathic inflammatory myopathy. Risk factors include statins, cancer, connective tissue diseases, autoimmune diseases, and infections such as HIV2. Diagnosis includes clinical features, serum creatine kinase, HMG CoA reductase antibody (HMGCR-Ab), electromyography, and muscle biopsy. The first-line treatment options are steroids and immunosuppressive agents. Early use of immunoglobulin achieves good outcome. It is still under investigation for the recommended choice for immunosuppressive therapy and the duration of the therapy.
Implementation of a β-lactam therapeutic drug monitoring program: Experience from a large academic medical center
Authors: Venugopalan Veena , Hamza Malva , Santevecchi Barbara , DeSear Kathryn , Cherabuddi Kartikeya , Peloquin Charles A , Alshaer Mohammad H
Published: June 2022

Purpose

To describe the implementation and operationalization of a β-lactam (BL) therapeutic drug monitoring (TDM) program at a large academic center.

BLs are the most used class of antibiotics. Suboptimal antibiotic exposure is a significant concern in hospitalized patients, particularly in those with altered pharmacokinetics. BL-TDM provides clinicians the opportunity to optimize drug concentrations to ensure maximal therapeutic efficacy while minimizing toxicity. However, BL-TDM has not been widely adopted due to the lack of access to assays. The University of Florida Shands Hospital developed a BL-TDM program in 2015. This is a consultative service primarily run by pharmacists and is conducted in all patient care areas. An analysis was performed on the first BL-TDM encounter for 1,438 patients. BL-TDM was most frequently performed for cefepime (61%, n = 882), piperacillin (15%, n = 218), and meropenem (11%, n = 151). BL-TDM was performed a median of 3 days (interquartile range, 1-5 days) from BL initiation. Among patients with available minimum inhibitory concentration (MIC) values and trough concentrations, the pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT>MIC was attained in 308 patients (88%). BL-TDM resulted in a dosage adjustment in 25% (n = 361) of patients.

Conclusion

Implementation of a BL-TDM program requires the concerted efforts of physicians, pharmacists, nursing staff, phlebotomists, and personnel in the analytical laboratory. Standard antibiotic dosing failed to achieve optimal PK/PD targets in all patients; utilizing BL-TDM, dose adjustments were made in 1 of every 4 patients.
Longitudinal alterations in gamma-aminobutyric acid (GABAA) receptor availability over ∼ 1 year following traumatic brain injury
Authors: Kang Y , Jamison K , Jaywant A , Dams-O’Connor K , Kim N , Karakatsanis N A , Butler T , Schiff N D , Kuceyeski A , Shah S A
Published: June 2022

Longitudinal alterations of gamma-aminobutyric acid (GABAA) receptor availability following traumatic brain injury have remained uncharacterized and may reflect changes in neuronal structure and function linked to cognitive recovery. We measured GABAA receptor availability using the tracer [11C]flumazenil in nine adults with traumatic brain injury (3–6 months after injury, subacute scan) and in 20 non-brain-injured individuals. A subset of subjects with traumatic brain injury (n = 7) were scanned at a second chronic time-point, 7–13 months after their first scan; controls (n = 9) were scanned for a second time, 5–11 months after the first scan. After accounting for atrophy in subjects with traumatic brain injury, we find broad decreases in GABAA receptor availability predominantly within the frontal lobes, striatum, and posterior-medial thalami; focal reductions were most pronounced in the right insula and anterior cingulate cortex (p < 0.05). Greater relative increase, compared to controls, in global GABAA receptor availability appeared between subacute and chronic scans. At chronic scan (>1 year post-injury), we find increased pallidal receptor availability compared to controls. Conversely, receptor availability remained depressed across the frontal cortices. Longitudinal improvement in executive attention correlated with increases in receptor availability across bilateral fronto-parietal cortical regions and the anterior-lateral aspects of the thalami. The specific observations of persistent bi-frontal lobe reductions and bilateral pallidal elevation are consistent with the anterior forebrain mesocircuit hypothesis for recovery of consciousness following a wide range of brain injuries; our results provide novel correlative data in support of specific cellular mechanisms underlying persistent cognitive deficits. Collectively, these measurements support the use of [11C]flumazenil to track recovery of large-scale network function following brain injuries and measure response to therapeutics.
Changes in working memory brain activity and task-based connectivity after long-duration spaceflight
Authors: Salazar Ana Paula , McGregor Heather R , Hupfeld Kathleen E , Beltran Nichole E , Kofman Igor S , De Dios Yiri E , Riascos Roy F , Reuter-Lorenz Patricia A , Bloomberg Jacob J , Mulavara Ajitkumar P , Wood Scott J , Seidler RachaelD
Published: June 2022

We studied the longitudinal effects of approximately 6 months of spaceflight on brain activity and task-based connectivity during a spatial working memory (SWM) task. We further investigated whether any brain changes correlated with changes in SWM performance from pre- to post-flight. Brain activity was measured using functional magnetic resonance imaging while astronauts (n = 15) performed a SWM task. Data were collected twice pre-flight and 4 times post-flight. No significant effects on SWM performance or brain activity were found due to spaceflight; however, significant pre- to post-flight changes in brain connectivity were evident. Superior occipital gyrus showed pre- to post-flight reductions in task-based connectivity with the rest of the brain. There was also decreased connectivity between the left middle occipital gyrus and the left parahippocampal gyrus, left cerebellum, and left lateral occipital cortex during SWM performance. These results may reflect increased visual network modularity with spaceflight. Further, increased visual and visuomotor connectivity were correlated with improved SWM performance from pre- to post-flight, while decreased visual and visual-frontal cortical connectivity were associated with poorer performance post-flight. These results suggest that while SWM performance remains consistent from pre- to post-flight, underlying changes in connectivity among supporting networks suggest both disruptive and compensatory alterations due to spaceflight.
Decreasing microbiota-derived uremic toxins to improve CKD outcomes
Authors: Beker Braian M , Colombo Iara , Gonzalez-Torres Henry , Musso Carlos G
Published: June 2022

Chronic kidney disease (CKD) is set to become the fifth-leading global cause of death by 2040. This illustrates the many unknowns regarding its pathogenesis and therapy. A key unknown relates to the therapeutic impact of the interaction between CKD and the gut microbiome. The normal gut microbiome is essential for body homeostasis. There is evidence for multiple interactions between the microbiota and CKD—its causes, comorbidities and therapeutic interventions—that are only starting to be unraveled. Thus uremic retention products, such as urea itself, modify the gut microbiota biology and both dietary and drug prescriptions modify the composition and function of the microbiota. Conversely, the microbiota may influence the progression and manifestations of CKD through the production of biologically active compounds (e.g. short-chain fatty acids such as butyrate and crotonate) and precursors of uremic toxins. The present review addresses these issues and their relevance for novel therapeutic approaches ranging from dietary interventions to prebiotics, probiotics, synbiotics and postbiotics, to the prevention of the absorption of microbial metabolites and to increased clearance of uremic toxins of bacterial origin through optimized dialysis techniques or blockade of tubular cell transporters.
Work-Related Productivity Loss and Associated Indirect Costs in Patients With Crohn’s Disease or Ulcerative Colitis in the United States
Authors: Ding Zhijie , Muser Erik , Izanec James , Lukanova Rina , Kershaw James , Roughley Adam
Published: June 2022

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), affects an estimated 1.6 million US adults, and results in humanistic and economic burden even among mild patients, which grows with increasing disease activity.

Methods

Gastroenterologists and their IBD patients provided real-world data via US IBD Disease Specific Programmes 2014–2018. Patients with physician- and patient-reported data completing a Work Productivity and Activity Impairment questionnaire were categorized by disease activity, defined using Crohn’s Disease Activity Index (CD) and partial Mayo scores (UC), respectively. Associations of disease activity with patient-reported productivity loss and indirect costs were assessed.

Results

The analyses included 281 patients with CD and 282 patients with UC. Mean ages were 40.0 and 40.5 years, and mean disease durations 7.1 and 5.4 years, for CD and UC, respectively. In CD, absenteeism (0.95%–14.6%), presenteeism (11.7%–44.9%), and overall work impairment (12.4%–51.0%) increased with increasing disease activity (all P < .0001). In UC, absenteeism (0.6%–11.9%), presenteeism (7.1%–37.1%), and overall work impairment (7.5%–41.9%) increased with increasing disease activity (all P < .0001). Annual indirect costs due to total work impairment increased with increasing disease activity (all P < .0001), from $7169/patient/year (remission) to $29 524/patient/year (moderately-to-severely active disease) in CD and $4348/patient/year (remission) to $24 283/patient/year (moderately-to-severely active disease) in UC.

Conclusions

CD and UC patients experienced increased absenteeism, presenteeism, and overall work impairment with increasing disease activity, resulting in higher indirect costs. Treatments significantly reducing IBD disease activity could provide meaningful improvements in work productivity and associated costs.
Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes
Authors: Soler Artigas María , Sánchez-Mora Cristina , Rovira Paula , Vilar-Ribó Laura , Ramos-Quiroga Josep Antoni , Ribasés Marta
Published: June 2022

Background

Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits.

Methods

We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results.

Results

Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta = −0.058, 95% CrI = (−0.072, −0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (−0.048, −0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively].

Conclusions

Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories.
Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia
Authors: Cutts Julia C , O’Flaherty Katherine , Zaloumis Sophie G , Ashley Elizabeth A , Chan Jo Anne , Onyamboko Marie A , Fanello Caterina , Dondorp Arjen M , Day Nicholas P , Phyo Aung Pyae , Dhorda Mehul , Imwong Mallika , Fairhurst Rick M , Lim Pharath , Amaratunga Chanaki , Pukrittayakamee Sasithon , Hien Tran Tinh , Htut Ye , Mayxay Mayfong , Faiz M Abdul , Takashima Eizo , Tsuboi Takafumi , Beeson James G , Nosten Francois , Simpson Julie A , White Nicholas J , Fowkes Freya J I
Published: June 2022

Background

Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified.

Methods

In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere.

Results

Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2–7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, −0.14 to +0.40 hour) in DRC patients.

Conclusions

In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.
Stars as catalysts: an event-study analysis of the impact of star-scientist recruitment on local research performance in a small open economy
Authors: McHale John , Harold Jason , Mei Jen-Chung , Sasidharan Akhil , Yadav Anil
Published: June 2022

There is increasing interest among policymakers in small open economies in the use of star-scientist recruitment policies to catalyse the development of local clusters in targeted research areas. We use Scopus to assemble a dataset on over 1.4 million publications and subsequent citations for Denmark, Ireland and New Zealand from 1990 to 2017. An event-study model is used to estimate the dynamic effects of a star arrival on quality-adjusted research output at both the department and matched individual incumbent levels. Star arrivals are associated with statistically significant increases in department output (excluding the output of the star) of between 12% and 25% after 4 years. At the incumbent level, star arrivals lead to an approximately 5% increase in individual output, with substantially larger increases for incumbents who co-author with the star.