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The crystal structure of perfluorononanoic acid (PFNA) was solved via parallel tempering using synchrotron powder diffraction data obtained from the Brockhouse X-ray Diffraction and Scattering (BXDS) Wiggler Lower Energy (WLE) beamline at the Canadian Light Source. PFNA crystallizes in monoclinic space group P21/c (#14) with lattice parameters a = 26.172(1) Å, b = 5.6345(2) Å, c = 10.9501(4) Å, and β = 98.752(2)°. The crystal structure is composed of dimers, with pairs of PFNA molecules connected by hydrogen bonds via the carboxylic acid functional groups. The Rietveld-refined structure was compared to a density functional theory-optimized structure, and the root-mean-square Cartesian difference was larger than normally observed for correct powder structures. The powder data likely exhibited evidence of disorder which was not successfully modeled.
Background: The number of advanced practice providers (APPs)—nurse practitioners (NPs) and physician assistants (PAs)—continues to expand across the United States. Several studies suggest differences in antibiotic prescribing rates and appropriateness by APPs compared to physicians. The objective of this analysis is to characterize population- and provider-specific outpatient antibiotic prescribing rates among physicians and APPs nationally, by state, and within urban versus rural counties. Methods: We estimated outpatient oral antibiotic prescription rates for 2011 and 2022 using county-level prescription dispensing data from IQVIA Xponent® (numerator) and population census estimates (denominator). Provider specialty denominators were provided by IQVIA, based on data from the American Medical Association. Counties were classified as urban or rural per the 2013 National Center for Health Statistics classification. National and state-level prescription volume, rates per 1000 population, and average number of prescriptions per provider were calculated for physicians, NPs, and PAs. We assessed the degree to which provider-specific rates explained the variance of the overall rate by state, using the coefficient of determination (r2) from Pearson’s correlation. Results: Between 2011 and 2022, overall U.S. antibiotic prescribing declined from 877 to 709 per 1000 population, a 19.2% relative reduction. The provider-specific proportion of the overall prescribing rate relatively decreased by 32% for physicians but increased by 157% for APPs (NPs 229%, PAs 86%; Figure 1). State-level antibiotic prescribing rates varied by provider type for both years, shifting towards proportionally greater APP prescribing in 2022 (Figure 2). For 2011 and 2022, physician prescribing rate strongly correlated with the overall state rate (r2 = 0.83 in 2011 versus 0.80 in 2022), whereas the correlation of the NP prescribing rate increased (r2 = 0.20 in 2011 versus 0.76 in 2022). A total of 60,327 (7.2%) physicians practiced in rural settings in contrast to 42,876 (12%) NPs and 14,495 (9.4%) PAs in 2022. Providers in rural counties prescribed more antibiotics per provider on average compared to urban counties; rural physicians prescribed 57% more antibiotics per provider (207 vs 132 antibiotics per provider), rural NPs prescribed 115% more (284 vs 132), and rural PAs prescribed 53% more (289 vs 189). Conclusions: The relative contribution of APPs to outpatient antibiotic prescriptions more than doubled over the past decade, accounting for 1 in 3 prescriptions in 2022. This contribution was especially prominent among NPs in rural counties. Further evaluation of antibiotic prescribing appropriateness among APPs and integration of APPs into antibiotic stewardship efforts in various settings.
To quantify the proportion of referrals sent to Crumlin Cardiology Department for cardiac screening prior to commencement or modifying attention deficit hyperactivity disorder medication and assess the number detected with a clinically significant abnormality.
Methods:
A prospective audit was performed over a 6-month period, from November 2021 to April 2022 inclusive. Referrals sent via outpatient department triage letters, electrocardiogram dept. email, and walk-in electrocardiogram service were screened for those pertaining to commencing or modifying medication for children with attention deficit hyperactivity disorder. Each referral was coded against National Institute for Health and Care Excellence guidelines to determine the degree of clinical details given. Reported abnormalities, recommended management, and correspondence were recorded.
Results:
Ninety-one referrals were received during the 6-month audit period. More than half lacked a clinical indication for referral (53/91, 58.2%), with fewer than one third (26/91, 28.5%) meeting National Institute for Health and Care Excellence criteria for referral for cardiology. Eighty (80/91) referrals had clinical outcomes available for review (missing outpatient department information and age outside of service range accounted for eleven referrals with unavailable clinical outcomes). Of the eighty clinically reviewed referrals, seventy-two (72/80, 90%) were reported as normal with no cardiology follow up required. Eight referrals (8/80, 10%) were reviewed in the Cardiology Outpatient Department prior to commencement or modifying attention deficit hyperactivity disorder medication. Of these, only one (1/80 1%) had a clinically significant abnormality which was a potential contraindication to attention deficit hyperactivity disorder medication use, and this referral was appropriate as per National Institute for Health and Care Excellence guidelines.
Conclusion:
Routine screening prior to attention deficit hyperactivity disorder medication prescription in the absence of clinical indications (as per National Institute for Health and Care Excellence) contributed to delays in medication initiation among young people with attention deficit hyperactivity disorder. Unnecessary referrals have resource implications for cardiology clinical team. Improved adherence to National Institute for Health and Care Excellence guidelines would provide benefits for patients and clinicians.
Evidence for necrotising otitis externa (NOE) diagnosis and management is limited, and outcome reporting is heterogeneous. International best practice guidelines were used to develop consensus diagnostic criteria and a core outcome set (COS).
Methods
The study was pre-registered on the Core Outcome Measures in Effectiveness Trials (COMET) database. Systematic literature review identified candidate items. Patient-centred items were identified via a qualitative study. Items and their definitions were refined by multidisciplinary stakeholders in a two-round Delphi exercise and subsequent consensus meeting.
Results
The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management.
Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research.
Conclusion
The adoption of consensus-defined diagnostic criteria and COS facilitates standardised research reporting and robust data synthesis. Inclusion of patient and professional perspectives ensures best practice stakeholder engagement.
Although first identified 120 years ago, knowledge of the Toalean technoculture of Middle Holocene Sulawesi, Indonesia, remains limited. Previous research has emphasised the exploitation of largely terrestrial resources by hunter-gatherers on the island. The recent recovery of two modified tiger shark teeth from the Maros-Pangkep karsts of South Sulawesi, however, offers new insights. The authors combine use-wear and residue analyses with ethnographic and experimental data to indicate the use of these artefacts as hafted blades within conflict and ritual contexts, revealing hitherto undocumented technological and social practices among Toalean hunter-gatherers. The results suggest these artefacts constitute some of the earliest archaeological evidence for the use of shark teeth in composite weapons.
This paper outlines the ways in which the project is addressing the colonial legacy of Henry Wellcome as well as presenting the data from the first three field seasons at Jebel Moya, south-central Sudan. These data have substantially revised our chronological and socio-economic understanding of the site. Our excavations, initiated in 2017 and continued in 2019 and 2022, show a longer, more continuous occupation of the site than has been previously recognised. The faunal and botanical remains have implications for the spread of early domesticates in the eastern Sahel and for climate changes, and raise issues of resilience. There is confirmed human burial activity from at least the third millennium BC onwards, while the pottery continues to yield information about the variety of decoration and, for the final Assemblage 3, data on its usage. Overall, the continued importance of the site for the eastern Sahel is re-emphasised.
The development of wearable technology, which enables motion tracking analysis for human movement outside the laboratory, can improve awareness of personal health and performance. This study used a wearable smart sock prototype to track foot–ankle kinematics during gait movement. Multivariable linear regression and two deep learning models, including long short-term memory (LSTM) and convolutional neural networks, were trained to estimate the joint angles in sagittal and frontal planes measured by an optical motion capture system. Participant-specific models were established for ten healthy subjects walking on a treadmill. The prototype was tested at various walking speeds to assess its ability to track movements for multiple speeds and generalize models for estimating joint angles in sagittal and frontal planes. LSTM outperformed other models with lower mean absolute error (MAE), lower root mean squared error, and higher R-squared values. The average MAE score was less than 1.138° and 0.939° in sagittal and frontal planes, respectively, when training models for each speed and 2.15° and 1.14° when trained and evaluated for all speeds. These results indicate wearable smart socks to generalize foot–ankle kinematics over various walking speeds with relatively low error and could consequently be used to measure gait parameters without the need for a lab-constricted motion capture system.
Health staff in South Sudan and Nigeria face extreme risks while providing services: in 2021, at least 18 health care workers were killed in South Sudan and Nigeria, while 32 were kidnapped. Reporting of such incidents takes place via the WHO coordinated SS. However, such event reporting is not designed to capture “lower scale” security incidents, nor does it capture possible solutions. As such, the IRC in coordination with the Health Cluster and national organizations are conducting a survey to complement the existing analysis with insights of frontline health care workers, to support program design, funding requests, and advocacy activities. Research questions include:
What are the most common incidents of violence against health care workers?
What has been the impact of these incidents on staff well-being, on the health system/sector, and on access to health care for the wider community?
What are the priorities in preventing such incidents and reducing their impact?
Objectives:
To identify incidents of violence against health care as experienced by health care staff in 2022.
To identify health workers perspective on causes, impact, and what works in terms of prevention and response.
Method/Description:
A self-administered, online survey targeting all health staff working for the humanitarian community in South Sudan and Northeastern Nigeria.
Results/Outcomes:
This study is on-going with results expected by early September.
Conclusion:
This study is on-going with results expected by early September.
Caregiver mental health is linked to early childhood development, yet more robust evidence of community-based interventions to prevent maternal depression and optimize socio-emotional development of young children is needed. Objectives of this cluster-randomized controlled trial (cRCT), based in Northern Ghana, are to assess the impact of the lay counselor-delivered, group-based Integrated Mothers and Babies Course and Early Childhood Development (iMBC/ECD) program on (1) the mental health of mothers of children under age 2; and (2) the socio-emotional development of their children.
Methods
This cRCT randomized 32 women's groups – 16 received iMBC/ECD content (intervention) and 16 received general health education content (control). Surveys were administered at baseline, immediate post-intervention, and 8-month post-intervention. The primary outcome was maternal depression [Patient Health Questionnaire (PHQ-9)], and the secondary outcome was child's socio-emotional development [Ages and Stages Questionnaire: Social Emotional (ASQ:SE-2)]. Qualitative interviews with 33 stakeholders were also conducted.
Results
In total, 374 participants were enrolled at baseline while pregnant with the index child, 19% endorsing moderate/severe depression. Of these, 266 (71.1%) completed the 8-month post-intervention survey (~19 months post-baseline). There were no significant effects of iMBC/ECD on PHQ-9 and ASQ:SE-2 scores. However, results favored the intervention arm in most cases. iMBC participants were highly satisfied with the program but qualitative feedback from stakeholders indicated some implementation challenges.
Conclusions
This real-world evaluation had null findings; however, post-intervention depression levels were very low in both arms (3%). Future research should examine the potential impact of women's groups on postpartum mental health more broadly with varying content.
OBJECTIVES/GOALS: HIV-specific CD8+ T-cells play a critical role in partially controlling viral replication in infected-individuals, but ultimately fail to eliminate infection. Enhancing these T-cell responses through lymphocyte engineering approaches has the potential as a novel therapy capable of achieving durable control or eradication of infection. METHODS/STUDY POPULATION: IL-15 Superagonist (IL-15SA) potently supports the in vivo persistence and antiviral activity of adoptively transferred CD8+ T-cells. The Deep-PrimingTM technology platform, developed by Torque, allows for loading of immunomodulators onto the surface of T-cells via electrostatic ‘nanogels’, which slowly release to deliver sustained autocrine immune stimulation without the harmful effects of systemic exposure. Here, we investigate the impact of IL-15SA Deep-Priming on HIV-specific CD8+ T-cells in a humanized mouse model of HIV infection. Humanized mice were generated by engrafting NOD-scid-IL2Rgnull mice with memory CD4+ T-cells isolated from an ARV-suppressed HIV+ donor. An autologous HIV-specific Cytotoxic T-Lymphocyte (CTL) clone was isolated, and killing potential confirmed. Four weeks post humanization, mice were infected with HIV and received an infusion of unmodified HIV-Specific CTLs, or IL-15SA Deep-Primed HIV-specific CTLs (CTL-DP). T-cell numbers and plasma viral loads were quantified weekly by flow cytometry and qRT-PCR. RESULTS/ANTICIPATED RESULTS: Mice receiving unmodified CTLs trended toward reduced viral loads compared to the No Treatment condition, while mice receiving CTL-DP saw significant, 2-Log10 reductions in VL (p < 0.01). At 41 days post-infection 100% (5/5) of the No Treatment, 66.7% (4/6) of the CTL treatment, and 16.7% (1/6) of CTL-DP treatment mice had detectable viremia. IL-15SA Deep-Priming increased CTL expansion and persistence in peripheral blood which correlated with improved CD4+T-cell preservation. DISCUSSION/SIGNIFICANCE OF IMPACT: Here we demonstrate the first in vivo analysis of IL-15SA Deep-Priming of HIV-Specific CTLs. These data suggest that Deep-Priming of patient T-cells can enhance in vivo function and persistence, leading to improved viral suppression; a significant advancement in the field of HIV cure research. CONFLICT OF INTEREST DESCRIPTION: Austin Boesch, Thomas Andresen, and Douglas Jones are employees of Torque. Darrell Irvine is a co-founder of Torque and Chairman of Torque’s Scientific Advisory Board.
This report presents the latest data from ongoing excavations at Jebel Moya, Sudan. This year saw the opening of five new trenches and continued excavation of an archaeologically rich trench. We have recovered four individual burials, a mud brick wall and a number of animal and archaeobotanical remains. The excavations also yielded a longer pottery sequence, showing clearly that the site was in use by at least the sixth millennium BC. This season confirms the long and complex history of Jebel Moya and provides the material for future studies on population health and subsistence. This season also saw an increase in community engagement and a more detailed study of the various historical trajectories that make up the biography of Jebel Moya.
The coronavirus disease 2019 pandemic requires urgent modification to existing head and neck cancer diagnosis and management practices. A protocol was established that utilises risk stratification, early investigation prior to clinical review and a reduction in aerosol generating procedures to lessen the risk of coronavirus disease 2019 spread.
Methods
Two-week wait referrals were stratified into low, intermediate and high risk. Low risk patients were referred back to primary care with advice; intermediate and high risk patients underwent investigation. Clinical encounters and aerosol generating procedures were minimised. A combined diagnostic and therapeutic surgical approach was undertaken where possible.
Results
Forty-one patients were used to assess feasibility. Thirty-one per cent were low risk, 35 per cent were intermediate and 33 per cent were high risk. Thirty-three per cent were discharged with no imaging.
Conclusion
Implementing this protocol reduces the future burden on tertiary services, by empowering primary care physicians to re-refer low risk patients. The protocol is applicable across the UK and avoids diagnostic delay.
New excavations at the Jebel Moya cemetery in Sudan reveal extensive evidence for Meroitic-era occupation, providing valuable data on contemporaneous diet, migration, exchange and population composition in sub-Saharan Africa.
OBJECTIVES/SPECIFIC AIMS: According to the US census, there are 3.3 million Americans who have to use wheelchairs in order to maintain their mobility. About 50% of these patients develop a pressure ulcer at some point during their life time. Three major factors contribute to pressure ulceration; pressure, tissue temperature, and maceration due to sweating. The objective of this study is to develop a temperature regulating wheelchair cushion in order to address elevated tissue temperatures and related sweating. METHODS/STUDY POPULATION: We instrumented a wheelchair with cooling elements, a water filled cushion and a pump. The pump moves the water through the cooling elements where water temperature drops down to 15°C. The water then moves to the cushion where it cools the tissue and then back to the cooling elements. RESULTS/ANTICIPATED RESULTS: We recruited 1 healthy subject to sit on the instrumented wheelchair and then obtained thermographs of the cushion surface using an infrared thermal camera. After 1 minute of sitting on the cushion the minimum temperature was recorded as 27°C. After 10 minutes the temperature dropped to 23.3°C. DISCUSSION/SIGNIFICANCE OF IMPACT: In this ongoing proof-of-concept study we are investigating if circulating chilled water inside a wheelchair cushion is a feasible method to regulate tissue temperatures at the 25–28°C range. This range has been shown to delay ulceration under loading conditions that simulate sitting on a wheelchair. Initial results indicate that this may be an effective ulcer prevention method.
The magnetic and magnetocaloric properties of Ni45Mn43CoSn11 have been investigated using heat capacity measurements and magnetization with hydrostatic pressure applications. A shift in the martensitic transition temperature by 40 K to higher temperatures was observed with application of pressure P = 1.06 GPa. The magnetic entropy changes significantly increases from 24 to 42 J/kgK at pressure of 0.73 GPa. A large adiabatic temperature change of 4 K was found from specific heat measurements. Also, the density of states and Debye temperature has been estimated from heat capacity measurements. The mixed effects of pressure and magnetic field on the transition temperature are discussed.
Sedimentary charcoal particles from lakes are commonly used to investigate fire history. Fire-history reconstructions are based on measuring the surface area or counting the number of charcoal fragments in adjacent samples. Recently, the volume of charcoal particles was advised as a more accurate method for quantifying past charcoal production. Large charcoal datasets, used to synthesize global fire history, include these different types of charcoal measurements and implicitly assume that they provide comparable fire-history information. However, no study has demonstrated that this assumption is valid. Here we compare fire-frequency reconstructions based on measurements of charcoal area and number, and estimates of charcoal volume from two lake sediment records from the eastern Canadian boreal forest. Results indicate that the three proxies provide comparable fire-history interpretations when using a locally defined threshold to identify fire events.
Fire-history reconstructions inferred from sedimentary charcoal records are based on measuring sieved charcoal fragment area, estimating fragment volume, or counting fragments. Similar fire histories are reconstructed from these three approaches for boreal lake sediment cores, using locally defined thresholds. Here, we test the same approach for a montane Mediterranean lake in which taphonomical processes might differ from boreal lakes through fragmentation of charcoal particles. The Mediterranean charcoal series are characterized by highly variable charcoal accumulation rates. Results there indicate that the three proxies do not provide comparable fire histories. The differences are attributable to charcoal fragmentation. This could be linked to fire type (crown or surface fires) or taphonomical processes, including charcoal transportation in the catchment area or in the sediment. The lack of correlation between the concentration of charcoal and of mineral matter suggests that fragmentation is not linked to erosion. Reconstructions based on charcoal area are more robust and stable than those based on fragment counts. Area-based reconstructions should therefore be used instead of the particle-counting method when fragmentation may influence the fragment abundance.
In this manuscript, serial-shunt of square ring resonators with step-impedance open circuited stub resonators to produce a new on-off switchable bandpass to bandstop response in the same ultra-wideband microstrip filter structure is proposed. The closed ring of series-shunt square ring resonators with a combine stubs are introduced to excite the bandpass response while bandstop characteristic excited when gaps are embedded in the corners of the square ring resonators. The main advantage of this microstrip filter is its capability to switch from bandpass-to-bandstop operation using open-short gap, respectively. A microwave simulator is utilized to show the switchable case by replacing Skyworks radio frequency diodes (RF-PIN) instead of those gaps. The entire filter models have been simulated using the computer simulation technology (CST) Microwave Studio. The computed results for the proposed filters were compared with the measured results of the both prototype structures (bandpass- and bandstop-filter). The codes also showed good agreement between them. Other advantages include being small in size, and low in effective cost.