Hybrid motility mechanism of sperm at viscoelastic-solid interface.

To fertilize eggs, sperm must pass through narrow, complex channels filled with viscoelastic fluids in the female reproductive tract. While it is known that the topography of the surfaces plays a role in guiding sperm movement, sperm have been thought of as swimmers, i.e., their motility comes solely from sperm interaction with the surrounding fluid, and therefore, the surfaces have no direct role in the motility mechanism itself. Here, we examined the role of solid surfaces in the movement of sperm in a highly viscoelastic medium. By visualizing the flagellum interaction with surfaces in a microfluidic device, we found that the flagellum stays close to the surface while the kinetic friction between the flagellum and the surface is in the direction of sperm movement, providing thrust. Additionally, the flow field generated by sperm suggests slippage between the viscoelastic fluid and the solid surface, deviating from the no-slip boundary typically used in standard fluid dynamics models. These observations point to hybrid motility mechanisms in sperm involving direct flagellum-surface interaction in addition to flagellum pushing the fluid. This finding signifies an evolutionary strategy of mammalian sperm crucial for their efficient migration through narrow, mucus-filled passages of the female reproductive tract.

Translating microcalcification biomarker information into the laboratory: A preliminary assessment utilizing core biopsies obtained from sites of mammographic calcification.

Rationale and objectives: The potential of breast microcalcification chemistry to provide clinically valuable intelligence is being increasingly studied. However, acquisition of crystallographic details has, to date, been limited to high brightness, synchrotron radiation sources. This study, for the first time, evaluates a laboratory-based system that interrogates histological sections containing microcalcifications. The principal objective was to determine the measurement precision of the laboratory system and assess whether this was sufficient to provide potentially clinical valuable information. Materials and methods: Sections from 5 histological specimens from breast core biopsies obtained to evaluate mammographic calcification were examined using a synchrotron source and a laboratory-based instrument. The samples were chosen to represent a significant proportion of the known breast tissue, mineralogical landscape. Data were subsequently analysed using conventional methods and microcalcification characteristics such as crystallographic phase, chemical deviation from ideal stoichiometry and microstructure were determined. Results: The crystallographic phase of each microcalcification (e.g., hydroxyapatite, whitlockite) was easily determined from the laboratory derived data even when a mixed phase was apparent. Lattice parameter values from the laboratory experiments agreed well with the corresponding synchrotron values and, critically, were determined to precisions that were significantly greater than required for potential clinical exploitation. Conclusion: It has been shown that crystallographic characteristics of microcalcifications can be determined in the laboratory with sufficient precision to have potential clinical value. The work will thus enable exploitation acceleration of these latent microcalcification features as current dependence upon access to limited synchrotron resources is minimized.

Utilization of Primary Health Care Under National Health Insurance in Samarinda Municipality, East Kalimantan Province, Indonesia.

Aim: In Indonesia, basic community health services are provided to all citizens through Primary Health Care (PHC) settings under the National Health Insurance (NHI) scheme. The insurance is compulsory and provides basic community health needs. Based on a gatekeeper concept, the PHC is deemed to be the first contact point for all basic healthcare needs. Despite the commencement of services through PHC settings in 2014 under this concept, utilization in PHC settings remains lower than in hospital settings. This study aimed to assess factors associated with utilization of PHC under National Health Insurance in Samarinda Municipality, East Kalimantan Province, Indonesia. Materials and Methods: The research examined the utilization of services over six months. It employed a cross-sectional method and included 382 NHI participants in 10 districts of Samarinda Municipality. Each district was divided into urban and semi-urban areas based upon local government indicators representing the whole research area. A two-stage random sampling and purposive sampling approach was implemented to select the sample. The participants were interviewed using a structured questionnaire. Chi-square and multiple logistic regressions were conducted to determine the impact of factors on the utilization of PHC. Results: Only 17.3% of participants used PHC services regularly. Three constitutive factors, type of NHI participants (Adj. OR: 2.62; p<0.005), accommodation (Adj. OR: 2.18; p<0.005) and awareness (Adj. OR: 3.27; p<0.005) most profoundly influenced the under-utilization of PHC by NHI participants. Conclusion: The study found that the type of NHI participant and the utilization factors of accommodation and awareness significantly influenced the degree of utilization of PHC facilities by NHI participants and that the differences arose from variations in knowledge and experience. Strengthening these factors will rely upon an expanded role of government and community collaboration, emphasizing the needs of NHI participants.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Safety and Immunogenicity of Bivalent RSVpreF Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines. METHODS: The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy ≥65-year-olds in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein-based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% CI >0.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data. RESULTS: Of 1403 participants randomized, 1399 received vaccinations (median [range] age, 70 [65‒91] years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin. CONCLUSION: The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older adult population. CLINICAL TRIAL REGISTRATION: NCT05301322.

Plasma proteomic associations with genetics and health in the UK Biobank.

The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand-receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public-private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics1.

Benzodiazepine Use Disorder: Common Questions and Answers.

In the United States, more than 30 million adults have reported taking a benzodiazepine within the past year. Misuse-use of a drug in a way that a doctor did not direct-accounts for 17.2% of all benzodiazepine use. Family physicians face challenges when balancing the patient's perceived benefits of benzodiazepines with known risks and lack of evidence supporting their use. Benzodiazepines cause significant central nervous system-related adverse effects including sedation, confusion, memory loss, depression, falls, fractures, and motor vehicle crashes. Factors that increase the risk of adverse effects and misuse are other substance use disorders, using concomitant central nervous system medications, and central nervous system or pulmonary diseases. Compared with intermittent use, chronic daily use in older adults is associated with a higher risk of falls, fractures, hospitalizations, and death. Withdrawal symptoms such as anxiety, sleep disturbances, and agitation are common and often prolonged. Adjunctive treatment with antiepileptics, antidepressants, and pregabalin has been shown to lessen withdrawal symptoms. Deprescribing benzodiazepines for patients who use them chronically should be individualized with slow tapering over weeks to months, or longer, to minimize the intensity of withdrawal symptoms. Incorporating behavioral interventions, such as cognitive behavior therapy, improves deprescribing outcomes.

GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.

UK national trainee survey of hepatology training, research and the future workforce.

Objective: The increasing prevalence of liver disease in the UK means there is a pressing need to expand the hepatology workforce. This survey aims to evaluate current hepatology training provision, and trainee attitudes towards future careers in hepatology. Method: An electronic survey was distributed to higher specialty gastroenterology and hepatology trainees in the UK between March and May 2022. Results: 138 trainees completed the survey covering all training grades and regions of the UK. 73.7% reported receiving adequate hepatology training currently, with 55.6% intending to become future hepatologists. Trainee preference for future hepatology consultant posts in specialist liver centres were almost threefold higher compared with district general hospitals (60.9% vs 22.6%). All trainees, irrespective of training grade reported high confidence in managing decompensated cirrhosis in both inpatient and outpatient settings. Senior trainees (grade ST6 and higher), without advanced training programme (ATP) experience reported significantly lower confidence in managing viral hepatitis, hepatocellular carcinoma and post-transplant patients compared with equivalent trainees with ATP experience. For junior trainees (IMT3-ST5), remaining in their current deanery was the most important factor when considering future hepatology training application. Conclusions: There is a significant need to deliver widely available training on the management of complex liver disease to improve non-ATP trainee confidence. Innovative job planning strategies are required to encourage trainees to pursue careers outside of specialist liver centres. Expansion of hepatology training networks with wider geographical coverage are needed to address the growing need for more hepatologists around the UK.

Outcomes of National Survey of the Practice of Hepatocellular Carcinoma Surveillance.

Background & Aim: HCC has significantly improved outcomes when detected early. Guidelines recommend biannual surveillance with ultrasound (US) and/or AFP in at-risk individuals. This survey aimed to describe HCC surveillance adherence/practices amongst the NHS hospitals in the UK. Methods: An electronic survey was sent to 79 NHS hospitals via the British Association for the Study of the Liver distribution list. The responses were captured from July 2021 to January 2022. Centres were divided into hepato-pancreato-biliary (HPB) and non-HPB centres, depending on whether the hospital undertakes major liver surgeries. Results: A total of 39 (49.3%) centres responded: 15 HPB and 24 non-HPB centres from across the UK. HCC surveillance eligibility criteria were universally applied, but heterogeneous approaches occur outside these criteria. Eighty per cent of patients undergoing surveillance were estimated to have cirrhosis. Eighty-five per cent of centres do 6-monthly US and AFP requested by clinicians and liver clinical nurse specialists. Compliance was estimated at 80% but not routinely audited. In most centres, general sonographers and/or radiologists perform surveillance US scans without a standard reporting template, although structured reporting was viewed as desirable by the majority. Poor views on US are approached heterogeneously, with patients variably offered ongoing US, CT, or MRI with different protocols. Conclusion: Most responding NHS hospitals follow 6-monthly HCC surveillance guidance. Data recording is variable, with limited routine data collection regarding compliance, yield, and quality. Surveillance US is mostly performed by non-HPB specialists without standardised reporting. There is an inconsistent approach to poor views with US surveillance. Even in a universal healthcare system such as NHS, which is free at the point of care, delivery of HCC surveillance has not improved over the last decade and remains variable.

A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review.

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance (P<5×10-8) that map to 611 loci, of which 145 loci are previously unreported. We define eight non-overlapping clusters of T2D signals characterised by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial, and enteroendocrine cells. We build cluster-specific partitioned genetic risk scores (GRS) in an additional 137,559 individuals of diverse ancestry, including 10,159 T2D cases, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned GRS are more strongly associated with coronary artery disease and end-stage diabetic nephropathy than an overall T2D GRS across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings demonstrate the value of integrating multi-ancestry GWAS with single-cell epigenomics to disentangle the aetiological heterogeneity driving the development and progression of T2D, which may offer a route to optimise global access to genetically-informed diabetes care.

Exploration of utility of combined optical photothermal infrared and Raman imaging for investigating the chemical composition of microcalcifications in breast cancer.

Microcalcifications play an important role in cancer detection. They are evaluated by their radiological and histological characteristics but it is challenging to find a link between their morphology, their composition and the nature of a specific type of breast lesion. Whilst there are some mammographic features that are either typically benign or typically malignant often the appearances are indeterminate. Here, we explore a large range of vibrational spectroscopic and multiphoton imaging techniques in order to gain more information about the composition of the microcalcifications. For the first time, we validated the presence of carbonate ions in the microcalcifications by O-PTIR and Raman spectroscopy at the same time, the same location and the same high resolution (0.5 µm). Furthermore, the use of multiphoton imaging allowed us to create stimulated Raman histology (SRH) images which mimic histological images with all chemical information. In conclusion, we established a protocol for efficiently analysing the microcalcifications by iteratively refining the area of interest.

Development and Demonstration of a Wireless Ultraviolet Sensing Network for Dose Monitoring and Operator Safety in Room Disinfection Applications.

The use of mobile ultraviolet-C (UV-C) disinfection devices for the decontamination of surfaces in hospitals and other settings has increased dramatically in recent years. The efficacy of these devices relies on the UV-C dose they deliver to surfaces. This dose is dependent on the room layout, the shadowing, the position of the UV-C source, lamp degradation, humidity and other factors, making it challenging to estimate. Furthermore, since UV-C exposure is regulated, personnel in the room must not be exposed to UV-C doses beyond occupational limits. We proposed a systematic method to monitor the UV-C dose administered to surfaces during a robotic disinfection procedure. This was achieved using a distributed network of wireless UV-C sensors that provide real-time measurements to a robotic platform and operator. These sensors were validated for their linearity and cosine response. To ensure operators could safely remain in the area, a wearable sensor was incorporated to monitor the UV-C exposure of an operator, and it provided an audible warning upon exposure and, if necessary, ceased the UV-C emission from the robot. Enhanced disinfection procedures could then be conducted as items in the room could be rearranged during the procedure to maximise the UV-C fluence delivered to otherwise inaccessible surfaces while allowing UVC disinfection to occur in parallel with traditional cleaning. The system was tested for the terminal disinfection of a hospital ward. During the procedure, the robot was manually positioned in the room by the operator repeatedly, who then used feedback from the sensors to ensure the desired UV-C dose was achieved while also conducting other cleaning tasks. An analysis verified the practicality of this disinfection methodology while highlighting factors which could affect its adoption.

Current Management and Future Directions for Pulmonary Arterial Hypertension Associated with Congenital Heart Disease.

Current management of patients with congenital heart disease has increased their survival into adulthood. This is accompanied by potential cardiac complications, including pulmonary hypertension associated with congenital heart disease (PAH-CHD). PAH-CHD constitutes a challenging subgroup of pulmonary hypertension and requires expert management to improve quality of life and prognosis. Novel agents have shown a significant improvement in morbidity and mortality in patients with pulmonary arterial hypertension. However, the long-term effects of these medications on PAH-CHD patients remain somewhat uncertain, necessitating treatment plans largely founded on the clinical experience of the healthcare providers. The aim of this review is to summarize the current evidence and future perspectives regarding treatment strategies for PAH-CHD to help better guide management of this complex disease.

Taking a different road: following Ag25 and Au25 cluster activation via in situ differential pair distribution function analysis.

Synchrotron X-ray total scattering measurements and accompanying pair distribution function (PDF) analyses are an excellent characterization technique to complement both transmission electron microscopy (TEM) and extended X-ray absorption fine structure (EXAFS) spectroscopy methods for detailed structural studies of atom-precise metal clusters. Herein, we study the thermal activation of Au25(SR)18- and Ag25(SR)18- clusters on alumina supports via in situ differential PDF (dPDF) analyses to compare structural changes in the metal clusters upon thermal activation in air. The metal-metal interatomic distances in Au25(SR)18- and Ag25(SR)18- clusters as measured by the dPDF method are comparable with those measured via single-crystal crystallographic and EXAFS methods. Compared to EXAFS analysis, in situ dPDF data can also provide high-temperature, non-element specific, longer range structural information with excellent temporal resolution. TEM and dPDF results show that Ag25(SR)18 systems behave significantly differently than analogous Au25(SR)18 systems upon thermal activation. Atom-precise Au clusters on alumina supports show continuous growth in particle size with increasing activation temperature due to particle coalescence upon thermal deprotection, and grow to an average size of 11.2 ± 2.1 nm for samples thermally activated at 650 °C. Conversely, analogous Ag clusters on alumina supports show particle size growth to mid-sized particles (3.2 ± 0.4 nm) at activation temperatures of 450 °C, beyond which the Ag particles then undergo thermal degradation to give smaller Ag clusters with an average size of 1.4 ± 0.2 nm for samples thermally activated at 650 °C. The significant difference in the behaviours of atom-precise, thiolate-protected Au and Ag clusters upon thermal activation emphasizes the development of distinct activation protocols for different metal cluster systems.

Breast calcification micromorphology classification.

OBJECTIVES: The importance of consistent terminology in describing the appearance of breast calcifications in mammography is well recognised. Imaging of calcifications using electron microscopy is a globally growing field of research. We therefore suggest that the time is ripe to develop a lexicon of terms for classifying the micromorphology of breast calcifications. METHODS: Calcifications within a wide range of histological sections of breast tissue, both benign and malignant, were imaged by Scanning Electron Microscopy (SEM). These images were examined, and the micromorphology of calcifications present was grouped to create a classification system. RESULTS: Based on the appearance of the calcifications observed, we propose five main categories for classification of the micromorphology of breast calcifications, namely, Dense Homogenous, Punctulate, Banded, Spongy and Aggregate. CONCLUSIONS: Use of the descriptive categories outlined here will help to ensure consistency and comparability of published observations on the micromorphology of breast calcifications. ADVANCES IN KNOWLEDGE: This is the first time a lexicon and classification system has been proposed for the micromorphology of breast calcifications, as observed by scanning electron microscopy of histological sections. This will facilitate comparability of observed relationships between micromorphology, mammographic appearance, chemistry and pathology.

Hospital surface disinfection using ultraviolet germicidal irradiation technology: A review.

Ultraviolet germicidal irradiation (UVGI) technologies have emerged as a promising alternative to biocides as a means of surface disinfection in hospitals and other healthcare settings. This paper reviews the methods used by researchers and clinicians in deploying and evaluating the efficacy of UVGI technology. The type of UVGI technology used, the clinical setting where the device was deployed, and the methods of environmental testing that the researchers followed are investigated. The findings suggest that clinical UVGI deployments have been growing steadily since 2010 and have increased dramatically since the start of the COVID-19 pandemic. Hardware platforms and operating procedures vary considerably between studies. Most studies measure efficacy of the technology based on the objective measurement of bacterial bioburden reduction; however, studies conducted over longer durations have examined the impact of UVGI on the reduction of healthcare associated infections (HCAIs). Future trends include increased automation and the use of UVGI technologies that are safer for use around people. Although existing evidence seems to support the efficacy of UVGI as a tool capable of reducing HCAIs, more research is needed to measure the magnitude of these effects and to establish recommended best practices.

AMPLE: An R package for capacity building on fisheries harvest strategies.

Fisheries harvest strategies are formal frameworks that represent a best-practice approach for sustainable fisheries management. A key component of a harvest strategy is a 'pre-agreed rule', known as a harvest control rule (HCR), that sets fishing opportunities, e.g. catch limits, based on an estimate of fish stock status, e.g. estimated stock biomass. The harvest strategy development process is driven by stakeholders who are required to make a range of informed decisions, including on the selection of the preferred HCR. Capacity building may be required to facilitate the stakeholder engagement, particularly regarding the technical components of harvest strategies, including HCRs. The AMPLE package for R provides three interactive apps that support capacity building and stakeholder engagement on HCRs. These apps have been used during in-country national workshops around the western and central Pacific Ocean (WCPO) to support the development of harvest strategies for the Western and Central Pacific Fisheries Commission. These apps include several novel features: they take users from a gentle introduction to how HCRs work, to using methods for testing, comparing and selecting a preferred HCR from a suite of candidates. They include an introduction to the impact of uncertainty on the performance of an HCR, introduce performance indicators and discuss methods for selecting the preferred HCR based on management objectives. As such they provide a more detailed overview of HCRs than currently existing alternatives. These apps provide an effective platform for hands-on learning and have proven to be successful at supporting capacity building on HCRs in the WCPO. For example, using them for group activities and competitions stimulated productive discussions and increased understanding. As the model fishery in AMPLE is generic and not based on a real example, the apps will also be of interest to scientists, managers and stakeholders developing harvest strategies in other regions.