The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old.

OBJECTIVES: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84. METHODS: Immunocompetent adults who received any first booster ≥three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The concentrations of ancestral anti-spike immunoglobulin were summarised as the geometric mean concentrations (GMC). Reactogenicity and safety outcomes were captured. Additional analyses including neutralising antibodies were performed on a subset. ACTRN12622000238774. RESULTS: Between Mar 2022 and Aug 2023, 743 participants were recruited and had D28 samples; 155 belonged to the 50-<70y-AZD1222 stratum. The mean adjusted GMCs (95% credible intervals) were 20,690 (17 555-23 883), 23,867 (20 144-27 604) and 8654 (7267-9962) U/mL at D28 following boosting with BNT162b2, mRNA-1273 and NVX-CoV2372, respectively, and 10,976 (8826-13 196), 15,779 (12 512-19 070) and 6559 (5220-7937) U/mL by D84. IgG against Omicron BA.5 was 2.7-2.9 times lower than the ancestral strain. Limited neutralisation against Omicron subvariants was found following all vaccines. Severe reactogenicity events were <4%. CONCLUSIONS: All vaccines were immunogenic with more rapid waning after mRNA vaccines. These data support boosting with vaccines with greater specificity for circulating Omicron subvariants.

Update on elbow arthroplasties with emphasis on imaging.

Elbow arthroplasty is increasing in popularity and can be used to treat many conditions, such as trauma, primary and secondary osteoarthritis, inflammatory arthritis, and osteonecrosis. Total elbow arthroplasty (TEA) is reserved for patients with severe symptoms refractory to more conservative management. In addition to TEA, hemi-arthroplasty, interposition arthroplasty, and resection arthroplasty also play roles in the management of elbow pain. There are specific indications for each type of arthroplasty. Postoperative complications may occur with elbow arthroplasties and may be surgery or hardware related. Imaging is important in both pre-operative planning as well as in post-surgical follow-up. This article reviews the different types of elbow arthroplasties, their indications, their normal postoperative imaging appearances, and imaging findings of potential complications.

Risk, regulation and offshore windfarms: Ways to manage environmental uncertainty and over-precaution.

Globally there are concerns over a warming climate and the UK has declared a climate and ecological emergency and has an ambitious programme for the growth of offshore windfarms to contribute to commitments to achieving a legally binding Net Zero for greenhouse gas emissions by 2050. Offshore windfarm consenting is comparatively mature in the UK but evidence gaps to inform impact assessment and uncertainty to inform decision making has led to a precautionary approach that slows the speed of consent decisions. This paper examines the approach to UK offshore windfarm consenting, reviews the precautionary but risk-based approach that environmental decision makers have adopted in light of evidence gaps, and summarises how the collection of empirical data and reviews of evidence collected from operational windfarms has improved scientific knowledge and focussed decision making. A summary is also provided of the enduring legislative safeguards that apply during the lifetime of any consent and recommendations are made on the risk appetite that advisers and decision makers should adopt in view of policy that seeks to accelerate sectoral growth whilst enhancing nature recovery.

Southern ocean carbon and heat impact on climate.

The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Update on Shoulder Arthroplasties with Emphasis on Imaging.

Shoulder pain and dysfunction may significantly impact quality of life. If conservative measures fail, advanced disease is frequently treated with shoulder arthroplasty, which is currently the third most common joint replacement surgery following the hip and knee. The main indications for shoulder arthroplasty include primary osteoarthritis, post-traumatic arthritis, inflammatory arthritis, osteonecrosis, proximal humeral fracture sequelae, severely dislocated proximal humeral fractures, and advanced rotator cuff disease. Several types of anatomic arthroplasties are available, such as humeral head resurfacing and hemiarthroplasties, as well as total anatomic arthroplasties. Reverse total shoulder arthroplasties, which reverse the normal ball-and-socket geometry of the shoulder, are also available. Each of these arthroplasty types has specific indications and unique complications in addition to general hardware-related or surgery-related complications. Imaging-including radiography, ultrasonography, computed tomography, magnetic resonance imaging, and, occasionally, nuclear medicine imaging-has a key role in the initial pre-operative evaluation for shoulder arthroplasty, as well as in post-surgical follow-up. This review paper aims to discuss important pre-operative imaging considerations, including rotator cuff evaluation, glenoid morphology, and glenoid version, as well as to review post-operative imaging of the various types of shoulder arthroplasties, to include normal post-operative appearances as well as imaging findings of complications.

Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).

BACKGROUND: The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. METHODS: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer's Comirnaty, Moderna's Spikevax or Novavax's Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. DISCUSSION: PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

Longitudinal evaluation of laboratory-based serological assays for SARS-CoV-2 antibody detection.

Serological assays for SARS-CoV-2 infection are now widely available for use in diagnostic laboratories. Limited data are available on the performance characteristics in different settings, and at time periods remote from the initial infection. Validation of the Abbott (Architect SARS-CoV-2 IgG), DiaSorin (Liaison SARS-CoV-2 S1/S2 IgG) and Roche (Cobas Elecsys Anti-SARS-CoV-2) assays was undertaken utilising 217 serum samples from 131 participants up to 7 months following COVID-19 infection. The Abbott and DiaSorin assays were implemented into routine laboratory workflow, with outcomes reported for 2764 clinical specimens. Sensitivity and specificity were concordant with the range reported by the manufacturers for all assays. Sensitivity across the convalescent period was highest for the Roche at 95.2-100% (95% CI 81.0-100%), then the DiaSorin at 88.1-100% (95% CI 76.0-100%), followed by the Abbott 68.2-100% (95% CI 53.4-100%). Sensitivity of the Abbott assay fell from approximately 5 months; on this assay paired serum samples for 45 participants showed a significant drop in the signal-to-cut-off ratio and 10 sero-reversion events. When used in clinical practice, all samples testing positive by both DiaSorin and Abbott assays were confirmed as true positive results. In this low prevalence setting, despite high laboratory specificity, the positive predictive value of a single positive assay was low. Comprehensive validation of serological assays is necessary to determine the optimal assay for each diagnostic setting. In this low prevalence setting we found implementation of two assays with different antibody targets maximised sensitivity and specificity, with confirmatory testing necessary for any sample which was positive in only one assay.

Symptoms and laboratory manifestations of mild COVID-19 in a repatriated cruise ship cohort.

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31-45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.

Leptomeningeal Relapse of Embryonal Rhabdomyosarcoma after 15 years.

Aim Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour of childhood. We present the case of a late relapse of RMS to the leptomeninges after 15 years. Methods A 20 year old male presented with a 3 week history of headaches and nausea. He previously had RMS of his right ear diagnosed at age 5 years which was treated with concurrent chemoradiotherapy. An MRI Brain and Spine confirmed extensive leptomeningeal disease and CSF analysis confirmed the presence of recurrent embryonal RMS. Results He completed two cycles of cyclophosphamide and topotecan followed by 45Gy/25Fr of craniospinal radiotherapy. Conclusion Late relapses beyond five years can be seen in up to 9% of patients, however very late recurrences (>10 years) are exceedingly rare. Molecular based methods such as gene expression profiling can aid risk stratification and survivorship clinics may become increasingly useful in following patients with high risk features.

Paraneoplastic sarcoidosis: a review.

BACKGROUND: Sarcoidosis is occasionally seen in association with malignancy, both at the time of cancer diagnosis or during follow up. AIM: The purpose of this study is to identify patients with paraneoplastic sarcoid, their associated malignancies and disease characteristics. METHODS: We identified 289 patients diagnosed histologically with sarcoidosis over a 6-year period in one centre, from 2010 to 2016. Fifty of these patients had a prior or concomitant diagnosis of cancer. RESULTS: 17.3% of sarcoid cases had an associated malignancy. The most common malignancies were Gastrointestinal (20%), Haematological (18%), Lung (12%), Gynaecological (12%) and Head and Neck cancer (12%). 74% of sarcoid cases had pulmonary disease with sarcoid diagnostic tissue obtained most frequently via endobronchial ultrasound fine needle aspiration (68%). Most sarcoid cases (66%) were diagnosed within the first year of their malignancy diagnosis. DISCUSSION: Careful consideration needs to be given to the possibility that potential cancer recurrences suspected on imaging studies may indeed be sarcoid reactions.

Soft Tissue Sarcoma of the Hand and Wrist: Epidemiology and Management Challenges.

Soft tissue sarcomas (STSs) of the hand and wrist are rare and confer a unique set of management challenges. We present a 15-year review and discussion of the epidemiology, tumor characteristics, treatment, and reconstructive strategies for such cases presenting to our regional sarcoma service. Three case examples are described. Of 218 STSs of the upper limb, 17 involved the hand or wrist. Alveolar rhabdomyosarcoma, synovial, and myxofibrosarcoma were the most common ones. Two patients required amputation for recurrence. Eight patients required flap reconstruction, of which five were free flaps with no failures or wound healing complications. Two-year overall survival rate was 92%. Local recurrence occurred in 12%. Limb-sparing surgery is possible in most patients, although there is often a degree of functional loss due to the surgical resection, and complex multistage reconstruction may be required. These lesions are still often incidental or unexpected findings when patients are treated for a presumed benign swelling. Clinicians treating localized swellings of the hand and wrist should maintain vigilance toward the possibility of a sarcoma diagnosis, to avoid delays in definitive treatment.

In-process rheometry as a PAT tool for hot melt extrusion.

Real time measurement of melt rheology has been investigated as a Process Analytical Technology (PAT) to monitor hot melt extrusion of an Active Pharmaceutical Ingredient (API) in a polymer matrix. A developmental API was melt mixed with a commercial copolymer using a heated twin screw extruder at different API loadings and set temperatures. The extruder was equipped with an instrumented rheological slit die which incorporated three pressure transducers flush mounted to the die surface. Pressure drop measurements within the die at a range of extrusion throughputs were used to calculate rheological parameters, such as shear viscosity and exit pressure, related to shear and elastic melt flow properties, respectively. Results showed that the melt exhibited shear thinning behavior whereby viscosity decreased with increasing flow rate. Increase in drug loading and set extrusion temperature resulted in a reduction in melt viscosity. Shear viscosity and exit pressure measurements were found to be sensitive to API loading. These findings suggest that this technique could be used as a simple tool to measure material attributes in-line, to build better overall process understanding for hot melt extrusion.

The ClosER study: results from a three-year pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes, 2011-2014.

OBJECTIVES: Until the introduction of fidaxomicin, antimicrobial treatment for Clostridium difficile infection (CDI) was limited to metronidazole and vancomycin. The changing epidemiology of CDI and the emergence of epidemic C. difficile PCR ribotype 027 necessitate continued surveillance to identify shifts in antibiotic susceptibility. ClosER, currently the largest pan-European epidemiological study of C. difficile ribotype distribution and antibiotic susceptibility, aimed to undertake antimicrobial resistance surveillance pre- and post-introduction of fidaxomicin. METHODS: Between July 2011 and July 2014, 39 sites across 22 European countries submitted 2830 C. difficile isolates for ribotyping, toxin testing and susceptibility testing to metronidazole, vancomycin, fidaxomicin, rifampicin, moxifloxacin, clindamycin, imipenem, chloramphenicol and tigecycline. RESULTS: Ribotypes 027, 014, 001, 078, 020, 002, 126, 015 and 005 were most frequently isolated, and emergent ribotypes 198 and 356 were identified in Hungary and Italy, respectively. All isolates were susceptible to fidaxomicin, with scarce resistance to metronidazole (0.2%, 6/2694), vancomycin (0.1%, 2/2694) and tigecycline (0%). Rifampicin, moxifloxacin and clindamycin resistance was evident in multiple ribotypes. Lack of ribotype diversity correlated with greater antimicrobial resistance. Epidemic ribotypes (027/001) were associated with multiple antimicrobial resistance, and ribotypes 017, 018 and 356 with high-level resistance. Additional factors may also influence local ribotype prevalence. CONCLUSIONS: Fidaxomicin susceptibility was retained post-introduction, and resistance to metronidazole and vancomycin was rare. Continued surveillance is needed, with more accurate classification and clarification of ribotype subtypes to further understand their role in the spread of resistance. Other factors may also influence changes in prevalence of C. difficile ribotypes with reduced antibiotic susceptibility.

Long-term variations of aerosol optical depth and aerosol radiative forcing over Iran based on satellite and AERONET data.

In this study, three different sensors of satellites including the Moderate Resolution Imaging Spectroradiometer (MODIS), Multi-angle Imaging SpectroRadiometer (MISR), and Total Ozone Mapping Spectrometer (TOMS) were used to study spatial and temporal variations of aerosols over ten populated cities in Iran. Also, the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model was used for analyzing the origins of air masses and their trajectory in the area. An increasing trend in aerosol concentration was observed in the most studied cities in Iran during 1979-2016. The cities in the western part of Iran had the highest annual mean of aerosol concentration. The highest aerosol optical depth (AOD) value (0.76 ± 0.51) was recorded in May 2012 over Ahvaz, and the lowest value (0.035 ± 0.27) was recorded in December 2013 over Tabriz. After Ahvaz, the highest AOD value was found over Tehran (annual mean 0.11 ± 0.20). The results show that AOD increases with increasing industrial activities, but the increased frequency of aerosols due to land degradation and desertification is more powerful in Iran. The trajectory analysis by the HYSPLIT model showed that the air masses come from Egypt, Syria, and Lebanon and passed over the Iraq and then reached to Iran during summer. Aerosol radiative forcing (ARF) has been analyzed for Zanjan (Aerosol Robotic Network site) during 2010-2013. The ARF at surface and top of the atmosphere was found to be ranging from - 79 to - 10W m-2 (average - 33.45 W m-2) and from - 25 to 6 W m-2 (average - 12.80 W m-2), respectively.

The introduction of radioactive seed localisation improves the oncological outcome of image guided breast conservation surgery.

INTRODUCTION: Radioactive seed localisation (RSL) has become increasingly popular for localisation of non-palpable breast tumours. This is largely due to advantages it offers in terms of practicality and convenience when compared to guide wire localisation (WL). This institute switched from using WL to RSL in September 2014. The primary aim was to assess whether this change improved the accuracy of excision with regards to inadequate margin rates and weight of excision specimens. The secondary aim was to establish whether there is a "learning curve" associated with RSL technique. METHODS: Retrospective data collection was performed for 333 consecutive cases of unifocal non-palpable invasive breast cancers undergoing excision with WL or RSL. An inadequate margin was defined as tumour <1 mm from an inked radial margin. Patient demographics, tumour characteristics and clinical outcomes were compared between WL and RSL cases. RESULTS: 100 WL and 233 RSL cases were included. Patient demographics and tumour characteristics were similar for both groups. Inadequate margin rates were 18% with WL and 8.6% with RSL (p = 0.013). Median specimen weights were 33.3 g with WL and 28.7 g with RSL (p = 0.014). Subdividing the RSL group into the first 100 cases performed (RSL1) and the subsequent 133 cases (RSL2), inadequate margin rates were 13.0% and 5.3% respectively (p = 0.037). Mean specimen weights were similar. CONCLUSION: Switching from WL to RSL results in a significant reduction in both inadequate margin rates and specimen weights. A procedure-specific learning curve is present on first implementation of RSL and following this, inadequate margin rates are further reduced.

Genome sequence variation among isolates of monkey B virus (Macacine alphaherpesvirus 1) from captive macaques.

Complete genome sequences of 19 strains of monkey B virus (Macacine alphaherpesvirus 1; BV) isolated from several macaque species were determined. A low level of sequence variation was present among BV isolates from rhesus macaques. Most variation among BV strains isolated from rhesus macaques was located in regions of repetitive or quasi-repetitive sequence. Variation in coding sequences (polypeptides and miRNAs) was minor compared to regions of non-coding sequences. Non-coding sequences in the long and short repeat regions of the genome did however exhibit islands of conserved sequence. Oral and genital isolates from a single monkey were identical in sequence and varied only in the number of iterations of repeat units in several areas of repeats. Sequence variation between BV isolates from different macaque species (different BV genotypes) was much greater and was spread across the entire genome, confirming the existence of different genotypes of BV in different macaque species.

"It's making contacts": notions of social capital and implications for widening access to medical education.

In the UK widening access (WA) activities and policies aim to increase the representation from lower socio-economic groups into Higher Education. Whilst linked to a political rhetoric of inclusive education such initiatives have however failed to significantly increase the number of such students entering medicine. This is compounded by a discourse that portrays WA applicants and students as lacking the essential skills or attributes to be successful in medical education. Much of the research in this area to date has been weak and it is critical to better understand how WA applicants and students negotiate medical admissions and education to inform change. To address this gap we amalgamated a larger dataset from three qualitative studies of student experiences of WA to medicine (48 participants in total). Inductively analysing the findings using social capital as a theoretical lens we created and clustered codes into categories, informed by the concepts of "weak ties" and "bridging and linking capital", terms used by previous workers in this field, to better understand student journeys in medical education. Successful applicants from lower socio-economic groups recognise and mobilise weak ties to create linking capital. However once in medical school these students seem less aware of the need for, or how to create, capital effectively. We argue WA activities should support increasing the social capital of under-represented applicants and students, and future selection policy needs to take into account the varying social capital of students, so as to not overtly disadvantage some social groups.