Rapid Iododeboronation with and without Gold Catalysis: Application to Radiolabelling of Arenes.

Radiopharmaceuticals that incorporate radioactive iodine in combination with single-photon emission computed tomography imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for the incorporation of radioiodine into small molecules. This work reports a rapid air- and moisture-stable ipso-iododeboronation procedure that uses NIS in the non-toxic, green solvent dimethyl carbonate. The fast reaction and mild conditions of the gold-catalysed method led to the development of a highly efficient process for the radiolabelling of arenes, which constitutes the first example of an application of homogenous gold catalysis to selective radiosynthesis. This was exemplified by the efficient synthesis of radiolabelled meta-[125 I]iodobenzylguanidine, a radiopharmaceutical that is used for the imaging and therapy of human norepinephrine transporter-expressing tumours.

Chirality Transfer in Gold(I)-Catalysed Hydroalkoxylation of 1,3-Disubstituted Allenes.

Gold(I)-catalysed intermolecular hydroalkoxylation of enantioenriched 1,3-disubstituted allenes was previously reported to occur with poor chirality transfer due to rapid allene racemisation. The first intermolecular hydroalkoxylation of allenes with efficient chirality transfer is reported here, exploiting conditions that suppress allene racemisation. A full substrate scope study reveals that excellent regio- and stereoselectivities are achieved when a σ-withdrawing substituent is present.

Ionised calcium levels in major trauma patients who received blood in the Emergency Department.

BACKGROUND: Exsanguination and coagulopathy remain one of the leading causes of preventable trauma related death. Low ionised calcium levels have been associated with hypotension and increased mortality and may inhibit clot formation. Blood product contains citrate that acts as a chelating agent. We hypothesised that trauma patients who have bled are at risk of hypocalcaemia and that receiving any amount of blood product can exacerbate this state. METHODS: A retrospective cohort analysis was performed on all trauma patients who had received early blood product in the ED of a single urban major trauma centre in the UK between 2013 and 2014. Ionised calcium levels were taken from venous blood gases from before and after blood product had been transfused. RESULTS: The study included 55 patients; 36 male (65%), age 33 (16-92) years, median injury severity score (ISS) 24 (4-50), units of blood product received 2 (1-16), overall mortality 18%. Fifty-five per cent patients were hypocalcaemic on arrival, 89% patients were hypocalcaemic after receiving any amount of blood product. There was a statistically significant difference in ionised calcium levels after receiving blood product, pretransfusion 1.11 mmol/L (95% CI 1.09 to 1.14), post-transfusion 0.98 mmol/L (95% CI 0.93 to 1.02) (p<0.001). A fall in calcium was seen after receiving just one unit and the more units of blood product received the greater the fall seen. CONCLUSIONS: Trauma patients that have sustained blood loss are at risk of hypocalcaemia. Ionised calcium levels fall significantly further even after receiving a small amount of blood product. Prompt recognition and early targeted treatment is needed from arrival.

Gold-Catalyzed Proto- and Deuterodeboronation.

A mild gold-catalyzed protodeboronation reaction, which does not require acid or base additives and can be carried out in "green" solvents, is described. As a result, the reaction is very functional-group-tolerant, even to acid- and base-sensitive functional groups, and should allow for the boronic acid group to be used as an effective traceless directing or blocking group. The reaction has also been extended to deuterodeboronations for regiospecific ipso-deuterations of aryls and heteroaryls from the corresponding organoboronic acid. Based on density functional theory calculations, a mechanism is proposed that involves nucleophilic attack of water at boron followed by rate-limiting B-C bond cleavage and facile protonolysis of a Au-σ-phenyl intermediate.

COVID-19: responding to a pandemic on Operation TORAL.

Operation TORAL was the UK's contribution to NATO's Operation RESOLUTE SUPPORT in Kabul, Afghanistan. Approximately 1000 British troops were deployed in Kabul when the arrival of the COVID-19 pandemic in Afghanistan was declared. This article will describe the challenges faced due to COVID-19 in Kabul.Medical planning considerations, occupational health issues, implementation of behaviour change and operating as part of a multinational organisation are all discussed, with challenges encountered detailed and potential solutions offered. The use of a suggested framework for ensuring the medical estimate process covered all areas relevant to an emerging viral pandemic -the 4Ds and 4Cs approach-proved particularly useful in the early stages of the pandemic in Afghanistan.

Abdominal aortic junctional tourniquet (AAJT-S): a systematic review of utility in military practice.

INTRODUCTION: Haemorrhage is the leading cause of potentially survivable death on the battlefield. Despite overall improvement in battlefield mortality, there has been no improvement in survival following non-compressible torso haemorrhage (NCTH). The abdominal aortic junctional tourniquet-stabilised (AAJT-S) is a potential solution that may address this gap in improving combat mortality. This systematic review examines the evidence base for the safety and utility of the AAJT-S for prehospital haemorrhage control in the combat setting. METHODS: A systematic search of MEDLINE, Cumulated Index to Nursing and Allied Health Literature and Embase (inception to February 2022) was performed using exhaustive terms, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The search was limited to English-language publications in peer-reviewed journals; grey literature was not included. Human, animal and experimental studies were included. Papers were reviewed by all authors to determine inclusion. Each study was assessed for level of evidence and bias. RESULTS: 14 studies met the inclusion criteria: 7 controlled swine studies (total n=166), 5 healthy human volunteer cases series (total n=251), 1 human case report and 1 mannikin study. The AAJT-S was demonstrated to be effective at cessation of blood flow when tolerated in healthy human and animal studies. It was easy to apply by minimally trained individuals. Complications were observed in animal studies, most frequently ischaemia-reperfusion injury, which was dependent on application duration. There were no randomised controlled trials, and the overall evidence base supporting the AAJT-S was low. CONCLUSIONS: There are limited data of safety and effectiveness of the AAJT-S. However, there is a requirement for a far-forward solution to improve NCTH outcomes, the AAJT-S is an attractive option and high-quality evidence is unlikely to be reported in the near future. Therefore, if this is implemented into clinical practice without a solid evidence base it will need a robust governance and surveillance process, similar to resuscitative endovascular balloon occlusion of the aorta, with regular audit of use.

Killed in action (KIA): an analysis of military personnel who died of their injuries before reaching a definitive medical treatment facility in Afghanistan (2004-2014).

INTRODUCTION: The majority of combat deaths occur before arrival at a medical treatment facility but no previous studies have comprehensively examined this phase of care. METHODS: The UK Joint Theatre Trauma Registry was used to identify all UK military personnel who died in Afghanistan (2004-2014). These data were linked to non-medical tactical and operational records to provide an accurate timeline of events. Cause of death was determined from records taken at postmortem review. The primary objective was to report time between injury and death in those killed in action (KIA); secondary objectives included: reporting mortality at key North Atlantic Treaty Organisation timelines (0, 10, 60, 120 min), comparison of temporal lethality for different anatomical injuries and analysing trends in the case fatality rate (CFR). RESULTS: 2413 UK personnel were injured in Afghanistan from 2004 to 2014; 448 died, with a CFR of 18.6%. 390 (87.1%) of these died prehospital (n=348 KIA, n=42 killed non-enemy action). Complete data were available for n=303 (87.1%) KIA: median Injury Severity Score 75.0 (IQR 55.5-75.0). The predominant mechanisms were improvised explosive device (n=166, 54.8%) and gunshot wound (n=96, 31.7%).In the KIA cohort, the median time to death was 0.0 (IQR 0.0-21.8) min; 173 (57.1%) died immediately (0 min). At 10, 60 and 120 min post injury, 205 (67.7%), 277 (91.4%) and 300 (99.0%) casualties were dead, respectively. Whole body primary injury had the fastest mortality. Overall prehospital CFR improved throughout the period while in-hospital CFR remained constant. CONCLUSION: Over two-thirds of KIA deaths occurred within 10 min of injury. Improvement in the CFR in Afghanistan was predominantly in the prehospital phase.

Impacts of Mobility Dogs on Kinematics during Ambulation: A Quantitative Study.

While prior research has explored various physiological consequences associated with assistive device use for ambulation, limited research has specifically explored the impact of mobility dog partnership on human kinematics. This descriptive study examined the impact of mobility dog partnership on kinematics of individuals in the normal young adult population. Sixteen participants were video recorded while walking in a straight line for 3.7 m (12 feet) under three different conditions (ambulating with no device, ambulating with a standard cane on the left side, and ambulating with a mobility dog on the left side). Differences between joint angles under each of the conditions were analyzed. Statistically significant differences were found in left elbow flexion when comparing ambulating with a cane versus ambulating with no device; left shoulder abduction when comparing ambulating with a cane versus ambulating with a mobility dog, ambulating with a mobility dog versus no device, and ambulating with a cane versus no device; and left hip extension when comparing ambulating with a mobility dog versus no device, and when ambulating with a mobility dog versus a cane. These findings suggest that providers should evaluate and monitor potential negative impacts of assistive devices such as mobility dogs on human kinematics.