The work presented in this paper represents a preliminary study on the performance of the new Silicon tracker layer, the Layer 0 (L0), that will be installed on top of the Alpha Magnetic Spectrometer (AMS-02), at the end of 2024. AMS-02 is a cosmic rays (CR) detector that has been operating on the International Space Stations (ISS) since May 2011. Thanks to its 9-layer Silicon tracker, this apparatus can perform high energy CR measurements with an unprecedented level of statistics and precision. However, high Z (Z $\ge 15$) CR nuclei statistic is strongly affected by fragmentation along the detector: with the installation of the new Silicon layer will be possible to achieve new unique high energy (TeV region) measures for those nuclei along with increased statistics for all nuclei up to Zinc. To achieve this, a Silicon ladder prototype, that will be part of the final Silicon layer, has been exposed to an ions test beam at the super-proton-synchrotron (SPS) of the CERN to characterize its charge resolution and the readout electronics. Preliminary results have shown a charge resolution of 10 $\%$ for nuclei up to Z=7.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Hypoxia is the main survival challenge that human beings encounter in high altitudes, it is also the leading cause of Acute Mountain Sickness (AMS). Studies have shown that hypoxia induces a large number of reactive oxygen species (ROS) in AMS patients, and the surge of ROS leads to the reduction of oxygen delivery capacity of erythrocyte, senescence and inflammatory impairment of erythrocyte and vascular endothelial cells to a certain extent. Through depicting a target-pathway network, our study indicates that Compound Danshen Dropping Pills (CDDP), which is one of the best-known traditional Chinese medicine used for the treatment of myocardial ischemic diseases, can improve red blood cell oxygen delivery capacity in AMS patients, alleviate tissue and organ damage, relieve a series of clinical symptoms caused by hypoxia through ROS clearance and related mechanisms. We further elucidate the active ingredients of CDDP targeting ROS related pathway by target-ingredient correspondence analysis. Tanshinone IIA, catechol and some other compounds of CDDP were identified to have certain targeting effect on ROS and ROS dependent pathways. This study provides new understandings of CDDP in clinical application on AMS.

We studied peat stratigraphy at the Mukhrino peatland, which is a typical ombrotrophic bog for the middle taiga zone of Western Siberia, to gain insights about its history, hydrology and carbon fluxes. Seven cores were collected from locations chosen to represent the typical present-day vegetation types, for dating of separated dissolved (DOC) and particulate (POC) organic carbon fractions using the Accelerator Mass Spectrometer (AMS) radiocarbon ($^{14}$C) method. The oldest peat was found at the bottoms of an underlying lake (10,053 cal. year BP) and an ancient riverbed (10,989 cal. year BP). For the whole history of the peatland the average peat accumulation rate was estimated to be 0.067±0.018 cm yr-1 (0.013-0.332 cm yr-1) and the carbon accumulation rate was 38.56±12.21 g m-2yr-1 (28.46–57.91 g m-2 yr-1). There were clear age differences between the separated samples of DOC and POC. DOC was older than POC in the uppermost 150 cm of the peat deposit, and younger in the deeper layers. The difference in age increased with depth, reaching 2,000–3,000 years at the bottom of the peat deposit (depth 430--530 cm). Following consideration of a range of factors that could potentially cause the dating discrepancy, we hypothesised that DOC continuously moves down into the mineral sediment beneath the peat, as an additional carbon flux that results in mixing of younger and older carbon. On this basis we estimated the apparent rate of DOC downward movement and the associated rate of carbon loss. The first estimate of the average rate of DOC downward movement in Western Siberia is 0.047±0.019 cm yr-1.

The 21st century, where all things are depending upon technology, almost all the human tasks are being done with the help of technology to save a lot of time and make our life much more comfortable. The monitoring of students’ attendance is a crucial task for faculty in today’s world. There are more chances of errors while entering the students’ attendance records in the primary system, primarily when the class was over. The main concern of this study is to build an IoT-based automated attendance management system for educational institutes by biometric recognition to incorporate fake/proxy attendance and errors of entry and to replace old manual methods of taking students’ attendance by calling their names or roll numbers. The AAS will click the image of the classroom, and it will automatically detect the faces of students sitting in the lecture room and recognize them during lectures then mark their attendance daily to keep a record of their presence and also maintain and manage it for the management staff of the institution for future by using web services.

Background/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates treatment of skin and soft tissue infections (SSTI). It was previ-ously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator, complement peptide-derived immunostimulant-02 (CPDI-02; formerly EP67), increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6- or 24-hrs post-challenge. Dermal abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in dermal abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity was determined by IM dose escalation and repeat IM dosing in male and female CD-1 mice. Results: Repeat IM treatment with CPDI-02 starting at 6-hrs post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolu-tion, whereas repeat treatment by the topical, SQ, or IV route had no effect. Starting CPDI-02 treatment at 24-hrs post-challenge was ineffective regardless of route. Single IM treatment with CPDI-02 starting at 6-hrs post-challenge was as effective as repeat IM treatment, increased systemic exposure, and decreased initial levels of IL-1β and increased MP in dermal abscesses. CPDI-02 was tolerated to between 130-170 mg/kg for single IM dosing and 65-130 mg/kg for repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA or other pathogens controlled by activated MP.

COVID-19 pandemic-related pressures on primary care may have driven inappropriate continuation of antibiotic prescriptions. Yet prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. Using the OpenSAFELY-TPP analytics platform, we analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between Jan 2020–2022. In-depth analysis was conducted on Jan 2020 (“pre-pandemic”) and Jan 2021 (“pandemic”) cohorts. Per-patient prescribing and clinical conditions were determined by searching primary care record data using clinical code lists. Repeat prescribing was defined as >=3 prescriptions in a 6 month lookback period. Associations between demographics (e.g. age, sex, geography) and repeat/non-repeat prescribing were explored using unadjusted risk ratios. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines -26% vs -11%, respectively). In the pandemic cohort, older patients were at higher risk of prescribing (especially repeat prescribing). The most common clinical conditions for repeat prescribing were COPD comorbidity and urinary tract infection. Comorbidities were more common among repeat vs non-repeat prescribed patients. In the pandemic cohort, vs pre-pandemic, repeat and non-repeat prescribing for comorbidities generally declined less compared with shorter-term conditions (infections, including COPD exacerbation/lower respiratory tract infection). Our findings inform ongoing development of stewardship interventions in England..

Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.

Cahuachi (Nazca River Valley, South Peru) was the major ceremonial center of the Nasca civilization. According to previous studies, it was struck and destroyed by three El Niño-Southern Oscillation events, which would have occurred around 100 BCE, 600 CE and 1000 CE, respectively. At the end of the series of events, the ceremonial center would have been buried by a cap of conglomerates. Despite this hypothesis raised well-founded doubts regarding its geochronological and paleoenvironmental implications, it is uncritically used as a reference in geoarchaeological research. In the present study, optically stimulated luminescence (OSL) dating results of some samples taken from alluvial deposits at Cahuachi are reported, with the aim to evaluate the literature’s hypothesis. Since the obtained ages are older than the Holocene epoch, such a hypothesis must be rejected. A number of field evidences corroborate this result. Finally, the advancement in fluvial geomorphology knowledge of the Nazca River Valley is briefly discussed.

This service improvement project was carried out at LEKMA Hospital, Ghana. Ghana has high levels of antimicrobial resistance (AMR). There is an urgent need to introduce models of care that optimize antibiotic prescribing. Methods Delayed / back-up prescribing is a strategy that could reduce antibiotic use in suspected upper respiratory tract infections. Four different models of delayed / back-up prescribing [no prescription; post-dated prescription (given to patient); post-dated prescription (forwarded to pharmacy); and follow-up appointment for reassessment after 3 days] were implemented in discussion between clinician and patient. Patients were contacted 10 days after their appointment to record compliance, check on their wellbeing, and rate their experience. Results Over a 3-month period (12/2019-02/2020), 142 patients were eligible for delayed / back-up prescribing. The most common clinical diagnoses were sore throat (102/140, 73%), common cold (22/140, 16%) and sinusitis (10/140, 7%). In total, 12 (9%) patients remained symptomatic at day 10, and only one individual in the entire cohort took antibiotics. Most patients (95%) rated their experience as good or very good. Conclusions Delayed / back-up prescribing models can lead to substantial reduction in antibiotic consumption amongst outpatient department patients with suspected upper respiratory tract infections. Delayed / back-up prescribing can be implemented safely in low and middle-income countries.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.