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Background: Point-of-care ultrasound (POCUS) education has become an essential component of medical school curricula. Ultrasound represents a highly effective teaching modality to reinforce anatomical knowledge gained during cadaveric dissections. At Texas Tech University Health Sciences Center-School of Medicine (TTUHSC-SOM), POCUS was incorporated into the pre-clerkship curriculum especially during the first year of medical school anatomy course., Methods: Pre- and post-ultrasound quizzes and summative exam performance were used to evaluate ultrasound session effectiveness. Post-block survey results were utilized to assess students' perception of these sessions., Results: A significant increase in post-quiz scores compared to pre-quiz scores (p < 0.0001) was observed in all three ultrasound sessions. Students ranked the overall experience with ultrasound sessions highly with 86% indicating ultrasound training was valuable in understanding human anatomy. Additionally, 92% indicated being more at ease in acquiring ultrasound images as the block progressed., Conclusions: First-year medical students perceived ultrasound training as valuable in enhancing their understanding of human anatomy and became more proficient acquiring ultrasound images as the block progressed. Early introduction of POCUS in the pre-clerkship curriculum helps build foundational knowledge and skills that support students in developing competency in image acquisition and interpretation., Competing Interests: Declarations. Ethics approval and consent to participate: This project has been approved by the TTUHSC-QIRB (Protocol number: QI-22091) as a quality improvement project. As the project involved the systematic collection and analysis of data to enhance the quality of an educational program, consent to participate was waived in accordance with TTUHSC QIRB guidelines and approval. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.

Tissue-specific gene expression is fundamental in development and evolution, and is mediated by transcription factors and by the cis-regulatory regions (enhancers) that they control. Transcription factors and their respective tissue-specific enhancers are essential components of gene regulatory networks responsible for the development of tissues and organs. Although numerous transcription factors have been characterized from different organisms, the knowledge of the enhancers responsible for their tissue-specific expression remains fragmentary. Here we use Ciona to study the enhancers associated with ten transcription factors expressed in the notochord, an evolutionary hallmark of the chordate phylum. Our results illustrate how two evolutionarily conserved transcription factors, Brachyury and Foxa2, coordinate the deployment of other notochord transcription factors. The results of these detailed cis-regulatory analyses delineate a high-resolution view of the essential notochord gene regulatory network of Ciona, and provide a reference for studies of transcription factors, enhancers, and their roles in development, disease, and evolution., (© 2024. The Author(s).)

Background: Clinical disease activity associated with inflammatory bowel disease (IBD) can place physical limitations on youths' activities of daily living. In turn, functional limitations potentially contribute to youths' heightened experience of IBD-induced intrusions on a wide range of routine and valued activities (i.e., illness intrusiveness), which can increase their risk for depressive symptoms. The present study examined the contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in youth with IBD., Methods: Youth (N = 180) completed the Functional Disability Inventory (FDI), Illness Intrusiveness Scale-Child (IIS-C), and Children's Depression Inventory-2 (CDI-2). Physicians completed the Physicians Global Assessment of disease activity (PGA)., Results: Results revealed a mediating effect for functional disability in the association between disease activity and depressive symptoms (PGA → FDI → CDI-2); illness intrusiveness mediated the association between functional disability and depressive symptoms (i.e., FDI → IIS-C → CDI-2). Serial mediation revealed that clinical disease activity conferred an indirect effect on youth depressive symptoms through the sequential effects of functional disability and illness intrusiveness (i.e., PGA → FDI → IIS-C → CDI-2)., Conclusions: Taken together, these findings indicate that youth who encounter more physical limitations as a function of clinical disease activity are more likely to experience an amplified sense of IBD-related intrusions on their ability to participate in meaningful activities. In turn, heightened illness intrusiveness increases the likelihood of depressive symptoms. Clinical interventions that help youth maintain adequate functional ability in the face of IBD disease activity and encourage involvement in positively valued activities could decrease the negative impact of IBD on youths' emotional adjustment., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

We investigated a secondary school (11-16 year-olds), a primary school (5-11 year-olds), reception year (4-5 year-olds) and a nursery (2-5 year-olds) following confirmed monkeypox in an adult in each educational setting during June and July 2022. MVA-BN vaccine was offered up to 14 days post exposure to 186 children < 12 years and 21 were vaccinated. No secondary cases occurred among at least 340 exposed students and more than 100 exposed staff during the 28-day follow-up period.

Purpose: Severe upper limb injuries can result in devastating consequences to functional and psychological well-being. Primary objectives of this review were to evaluate indications for amputation versus limb salvage in upper limb major trauma and whether any existing scoring systems can aid in decision-making. Secondary objectives were to assess the functional and psychological outcomes from amputation versus limb salvage., Methods: A systematic review was carried out in accordance with PRISMA guidelines. A search strategy was conducted on the MEDLINE, EMBASE, and Cochrane databases. Quality was assessed using the ROBINS-I tool. The review protocol was registered in PROSPERO., Results: A total of 15 studies met inclusion criteria, encompassing 6113 patients. 141 underwent primary amputation and 5972 limb salvage. General indications for amputation included at least two of the following: uncontrollable haemodynamic instability; extensive and concurrent soft tissue, bone, vascular and/or nerve injuries; prolonged limb ischaemia; and blunt arterial trauma or crush injury. The Mangled Extremity Severity Score alone does not accurately predict need for amputation, however, the Mangled Extremity Syndrome Index may be a more precise tool. Comparable patient-reported functional and psychological outcomes are seen between the two treatment modalities., Conclusions: Decision regarding amputation versus limb salvage of the upper limb is multifactorial. Current scoring systems are predominantly based on lower limb trauma, with lack of robust evidence to guide management of the upper extremity. Further high-quality studies are required to validate scoring systems which may aid in decision-making and provide further information on the outcomes from the two treatment options., (© 2021. The Author(s).)

Gene regulatory networks coordinate the formation of organs and structures that compose the evolving body plans of different organisms. We are using a simple chordate model, the Ciona embryo, to investigate the essential gene regulatory network that orchestrates morphogenesis of the notochord, a structure necessary for the proper development of all chordate embryos. Although numerous transcription factors expressed in the notochord have been identified in different chordates, several of them remain to be positioned within a regulatory framework. Here, we focus on Xbp1, a transcription factor expressed during notochord formation in Ciona and other chordates. Through the identification of Xbp1-downstream notochord genes in Ciona , we found evidence of the early co-option of genes involved in the unfolded protein response to the notochord developmental program. We report the regulatory interplay between Xbp1 and Brachyury, and by extending these results to Xenopus , we show that Brachyury and Xbp1 form a cross-regulatory subcircuit of the notochord gene regulatory network that has been consolidated during chordate evolution., Competing Interests: YW, AD, DJ, JK, LN, KB, JA, JS, AD No competing interests declared, (© 2022, Wu et al.)

A 25-year-old female presented with a chronic scapho-lunate ligament injury with development of carpal instability requiring reconstruction. During a standard dorsal longitudinal mid-line approach to the carpus, an extensor digitorum brevis manus (EDBM) muscle was found taking its origin from the dorsal wrist capsule overlying the lunate with innervation from the posterior interosseous nerve (PIN). Electrical stimulation of the muscle belly demonstrated abduction of the middle finger. The EDBM is a rare anatomical variant of the extensor compartment of the wrist and may be encountered during surgical approaches. Where possible these variant muscles should be carefully dissected off underlying structures, preserved and repaired at the conclusion of a procedure to ensure no perceived functional deficit to the patient. We present a case of a previously undescribed EDBM muscle function of pure finger abduction with no extension and a surgical technique of preserving its origin. We propose that the middle finger variant of the EDBM should be re-named the extensor digitorum brevis medius to reflect our findings., (© 2021. The Author(s).)

Effective spatio-temporal control of transcription and replication during S-phase is paramount to maintaining genomic integrity and cell survival. Dysregulation of these systems can lead to conflicts between the transcription and replication machinery, causing DNA damage and cell death. BRD4 allows efficient transcriptional elongation by stimulating phosphorylation of RNA polymerase II (RNAPII). We report that bromodomain and extra-terminal domain (BET) protein loss of function (LOF) causes RNAPII pausing on the chromatin and DNA damage affecting cells in S-phase. This persistent RNAPII-dependent pausing leads to an accumulation of RNA:DNA hybrids (R-loops) at sites of BRD4 occupancy, leading to transcription-replication conflicts (TRCs), DNA damage, and cell death. Finally, our data show that the BRD4 C-terminal domain, which interacts with P-TEFb, is required to prevent R-loop formation and DNA damage caused by BET protein LOF., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Validity and reproducibility of the clinician's eye (CE) to diagnose patella alta (PA) on a lateral knee radiography (radiograph) is unknown., Methods: Cross-sectional study of 46 lateral knee x-rays. Three blind observers used CE, Insall-Salvati (IS), modified Insall-Salvati (mIS), and Caton-Deschamps (C-D) to determine patellar height. Sensitivity and specificity of each observer was compared with the musculoskeletal radiologist's C-D measurements. Intraobserver and interobserver agreement were assessed with intraclass correlation coefficient and Fleiss κ, respectively. Time needed to estimate patellar height for every method was recorded in seconds. Statistical differences between observers were calculated with a generalized estimating equation. Analysis of variance and post hoc Bonferroni test compared duration of each method (P < 0.05). Data were analyzed using Stata 15 (StataCorp)., Results: CE, IS, mIS, and C-D's sensitivity and specificity values are as follows: 77%, 92%; 94%, 52%; 67%, 58%; and 53%, 89%, respectively. Intraclass correlation coefficient and Fleiss κ of CE, IS, mIS, and C-D values are as follows: 0.66 and 0.43, 0.88 and 0.68, 0.54 and 0.09, and 0.68 and 0.59, respectively. CE was the second most sensitive and most specific method for diagnosis of PA, with moderate intraobserver and interobserver agreement. IS was the most sensitive method with good intraobserver and interobserver agreement. CE was significantly faster (P < 0.05) than all other conventional radiographic ratios., Conclusion: CE's sensitivity increases with observer's experience and is highly specific. If normal patellar height is diagnosed, no other ratios are necessary, even in the less experienced clinician. Intraobserver and interobserver reproducibilities were moderate and only inferior to the IS ratio. In case patellar height is uncertain with the CE, the IS ratio is the most sensitive and reproducible method to confirm the diagnosis of PA.

Background: The dismal survival of glioblastoma (GBM) patients urgently calls for the development of new treatments. Chimeric antigen receptor T (CAR-T) cells are an attractive strategy, but preclinical and clinical studies in GBM have shown that heterogeneous expression of the antigens targeted so far causes tumor escape, highlighting the need for the identification of new targets. We explored if B7-H3 is a valuable target for CAR-T cells in GBM., Methods: We compared mRNA expression of antigens in GBM using TCGA data, and validated B7-H3 expression by immunohistochemistry. We then tested the antitumor activity of B7-H3-redirected CAR-T cells against GBM cell lines and patient-derived GBM neurospheres in vitro and in xenograft murine models., Findings: B7-H3 mRNA and protein are overexpressed in GBM relative to normal brain in all GBM subtypes. Of the 46 specimens analyzed by immunohistochemistry, 76% showed high B7-H3 expression, 22% had detectable, but low B7-H3 expression and 2% were negative, as was normal brain. All 20 patient-derived neurospheres showed ubiquitous B7-H3 expression. B7-H3-redirected CAR-T cells effectively targeted GBM cell lines and neurospheres in vitro and in vivo. No significant differences were found between CD28 and 4-1BB co-stimulation, although CD28-co-stimulated CAR-T cells released more inflammatory cytokines., Interpretation: We demonstrated that B7-H3 is highly expressed in GBM specimens and neurospheres that contain putative cancer stem cells, and that B7-H3-redirected CAR-T cells can effectively control tumor growth. Therefore, B7-H3 represents a promising target in GBM. FUND: Alex's Lemonade Stand Foundation; Il Fondo di Gio Onlus; National Cancer Institute; Burroughs Wellcome Fund., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Injuries to the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hand are particularly disabling. However, current standards for hand protection from blunt impact are not based on quantitative measures of the likelihood of damage to the tissues. The aim of this study was to evaluate the probability of injury of the MCP and PIP joints of the human hand due to blunt impact. Impact testing was conducted on 21 fresh-frozen cadaveric hands. Unconstrained motion at every joint was allowed. All hands were imaged with computed tomography and dissected post-impact to quantify injury. An injury-risk curve was developed for each joint using a Weibull distribution with dorsal impact force as the predictive variable. The injury risks for PIP joints were similar, as were those for MCP joints. The risk of injury of the MCP joints from a given applied force was significantly greater than that of the PIP joints (p = 0.0006). The axial forces with a 50% injury risk for the MCP and PIP joints were 3.0 and 4.2 kN, respectively. This is the first study to have investigated the injury tolerance of the MCP and PIP joints. The proposed injury curves can be used for assessing the likelihood of tissue damage, for designing targeted protective solutions such as gloves, and for developing more biofidelic standards for assessing these solutions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The ca. 1.38 billion years (Ga) old Roper Group of the McArthur Basin, northern Australia, is one of the most extensive Proterozoic hydrocarbon-bearing units. Organic-rich black siltstones from the Velkerri Formation were deposited in a deep-water sequence and were analysed to determine their organic geochemical (biomarker) signatures, which were used to interpret the microbial diversity and palaeoenvironment of the Roper Seaway. The indigenous hydrocarbon biomarker assemblages describe a water column dominated by bacteria with large-scale heterotrophic reworking of the organic matter in the water column or bottom sediment. Possible evidence for microbial reworking includes a large unresolved complex mixture (UCM), high ratios of mid-chained and terminally branched monomethyl alkanes relative to n-alkanes-features characteristic of indigenous Proterozoic bitumen. Steranes, biomarkers for single-celled and multicellular eukaryotes, were below detection limits in all extracts analysed, despite eukaryotic microfossils having been previously identified in the Roper Group, albeit largely in organically lean shallower water facies. These data suggest that eukaryotes, while present in the Roper Seaway, were ecologically restricted and contributed little to export production. The 2,3,4- and 2,3,6-trimethyl aryl isoprenoids (TMAI) were absent or in very low concentration in the Velkerri Formation. The low abundance is primary and not caused by thermal destruction. The combination of increased dibenzothiophene in the Amungee Member of the Velkerri Formation and trace metal redox geochemistry suggests that degradation of carotenoids occurred during intermittent oxygen exposure at the sediment-water interface and/or the water column was rarely euxinic in the photic zone and likely only transiently euxinic at depth. A comparison of this work with recently published biomarker and trace elemental studies from other mid-Proterozoic basins demonstrates that microbial environments, water column geochemistry and basin redox were heterogeneous., (© 2019 Commonwealth of Australia. Geobiology © 2019 John Wiley & Sons Ltd.)

The minimally invasive nature of wrist and small joint arthroscopy renders it particularly suitable for the application of the wide-awake local anesthesia no tourniquet (WALANT) technique. The application of WALANT wrist and small joint arthroscopy has given surgeons the ability to visualize both static and dynamic movements of a joint, to show the pathology and discuss with the patient, and to visualize a patient's repaired structures. This reinforces confidence in surgeons and encourages patients to comply with postoperative rehabilitation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

SF0166, a small-molecule α v β 3 antagonist, has physiochemical properties that allow distribution to the posterior segment of the eye after topical administration in an ophthalmic solution. The pharmacodynamics and ocular distribution of SF0166 were evaluated in several cell lines, chick chorioallantoic membrane assays, and models of ocular neovascularization in mice and pigmented rabbits. SF0166 inhibited cellular adhesion to vitronectin across human, rat, rabbit, and dog cell lines with IC 50 values of 7.6 pM to 76 nM. SF0166 inhibited integrin-ligand interactions at IC 50 values of 0.6-13 nM for human α v β 3 , α v β 6 , and α v β 8 SF0166 significantly decreased neovascularization in the oxygen-induced retinopathy mouse model. SF0166 distributed to the choroid and retina after topical ocular administration in amounts that substantially exceeded the cellular IC 50 for adhesion to vitronectin; drug concentrations were maintained for >12 hours. In the laser-induced choroidal neovascularization model, topical ocular administration of SF0166 decreased lesion area compared with vehicle and was comparable to a bevacizumab injection. In the vascular endothelial growth factor-induced early neovascularization and vascular leakage model, topical ocular application of SF0166 resulted in a dose-dependent reduction in vascular leakage; the highest ocular doses tested showed comparable activity to a bevacizumab injection., (Copyright © 2018 by The Author(s).)

Background: Elbow posterolateral rotatory instability occurs after an injury to the lateral collateral ligament complex (LCLC) in isolation or in association with an osteochondral fracture of the posterolateral margin of the capitellum (Osborne-Cotterill lesion [OCL]). The contribution to elbow stability of the posterolateral capsule, attached to this lesion, is unknown. This study quantified the displacement of the radial head on simulated posterior draw with sectioning of the posterior capsule (a simulated OCL) or LCLC., Methods: Biomechanical testing of the elbow was performed in 8 upper limb cadavers. With the elbow 0°, 30°, 60°, and 90° degrees of flexion, posterior displacement of the radius was measured at increments of a load of 5 N up to 50 N. A simulated OCL and LCLC injury was then performed., Results: A simulated OCL results in significantly more displacement of the radial head compared with the intact elbow at 30° to 60° of elbow flexion. LCLC resection confers significantly more displacement. An OCL after LCLC resection does not create further displacement., Conclusions: The degree of radial head displacement is greater after a simulated OCL at 30° to 60° of flexion compared with the intact elbow with the same load but not as great as seen with sectioning of the LCLC. This study suggests that the posterior capsule attaching to the back of the capitellum is important to elbow stability and should be identified as the Osborne-Cotterill ligament. Clinical studies are required to determine the importance of these biomechanical findings., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

In July 2005, four suicide bombers detonated explosive improvised high explosive devices (IEDs) in three separate underground carriages and a double decker bus in London, resulting in 56 deaths and 775 injured. This study aims to understand the mechanisms and patterns of burn injuries from high explosives, and the related factors that determine mortality. The types and patterns of burn injuries in survivors and fatalities in the confined underground train carriages and the bus were analysed, evaluating injury severity score and the victims' relative position from the detonation point. The data were sourced from collated police witness statements, hospital records, forensic post mortem examinations and forensic examinations at the scene. The detonation of an explosive device in a confined space causes complex injuries to the human body, resulting in blast-related direct thermal and radiant burns. Injury patterns and mortality were related to crowd density, enclosure design, position of the victims and proximity to the device. Suicide bombings using IEDs will result in direct thermal burns and radiant burns currently categorised in the quaternary (miscellaneous) blast injury group. We propose a classification of these burns following an analysis of the London bombing data with respect to burns in both the fatalities and survivors. Distance from the device, crowd density and environment influences these burns.

The annual meeting of the Society for Neuroscience (SfN) attracts over 30,000 attendees, including many of the world's most accomplished researchers. Although it can be intimidating to attend a conference of this scale, there are many rewards for undergraduates. Based on surveys of young neuroscientists, we provide planning strategies to ensure attendees maximize their exposure and retention of the breadth and depth offered by this large conference format without becoming overwhelmed.

Background: Alcohol use disorder (AUD) is a spectrum disorder characterized by mild to severe symptoms, including potential withdrawal signs upon cessation of consumption. Approximately five hundred thousand patients with AUD undergo clinically relevant episodes of withdrawal annually (New Engl J Med, 2003, 348, 1786). Recent evidence indicates potential for drugs that alter neuroimmune pathways as new AUD therapies. We have previously shown the immunomodulatory drugs, minocycline and tigecycline, were effective in reducing ethanol (EtOH) consumption in both the 2-bottle choice and drinking-in-the-dark paradigms. Here, we test the hypothesis that tigecycline, a tetracycline derivative, will reduce the severity of EtOH withdrawal symptoms in a common acute model of alcohol withdrawal (AWD) using a single anesthetic dose of EtOH in seizure sensitive DBA/2J (DBA) mice., Methods: Naïve adult female and male DBA mice were given separate injections of 4 g/kg i.p. EtOH with vehicle or tigecycline (0, 20, 40, or 80 mg/kg i.p.). The 80 mg/kg dose was tested at 3 time points (0, 4, and 7 hours) post EtOH treatment. Handling-induced convulsions (HICs) were measured before and then over 12 hours following EtOH injection. HIC scores and areas under the curve were tabulated. In separate mice, blood EtOH concentrations (BECs) were measured at 2, 4, and 7 hours postinjection of 4 g/kg i.p. EtOH in mice treated with 0 and 80 mg/kg i.p. tigecycline., Results: AWD symptom onset, peak magnitude, and overall HIC severity were reduced by tigecycline drug treatment compared to controls. Tigecycline treatment was effective regardless of timing throughout AWD, with earlier treatment showing greater efficacy. Tigecycline showed a dose-responsive reduction in acute AWD convulsions, with no sex differences in efficacy. Importantly, tigecycline did not affect BECs over a time course of elimination., Conclusions: Tigecycline effectively reduced AWD symptoms in DBA mice at all times and dosages tested, making it a promising lead compound for development of a novel pharmacotherapy for AWD. Further studies are needed to determine the mechanism of tigecycline action., (Copyright © 2016 by the Research Society on Alcoholism.)

Background: New pharmacotherapies to treat alcohol use disorders (AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice. To test the hypothesis that suppression of high EtOH consumption is a general property of tetracyclines, we screened several derivatives for antidrinking activity using the Drinking-In-the-Dark (DID) paradigm. Active drugs were studied further using the dose-response relationship., Methods: Adult female and male C57BL/6J mice were singly housed and the DID paradigm was performed using 20% EtOH over a 4-day period. Mice were administered a tetracycline or its vehicle 20 hours prior to drinking. Water and EtOH consumption was measured daily. Body weight was measured at the start of drug injections and after the final day of the experiment. Blood was collected for EtOH content measurement immediately following the final bout of drinking., Results: Seven tetracyclines were tested at a 50 mg/kg dose. Only minocycline and tigecycline significantly reduced EtOH drinking, and doxycycline showed a strong effect size trend toward reduced drinking. Subsequent studies with these 3 drugs revealed a dose-dependent decrease in EtOH consumption for both female and male mice, with sex differences in efficacy. Minocycline and doxycycline reduced water intake at higher doses, although to a lesser degree than their effects on EtOH drinking. Tigecycline did not negatively affect water intake. The rank order of potency for reduction in EtOH consumption was minocycline > doxycycline > tigecycline, indicating efficacy was not strictly related to their partition coefficients or distribution constants., Conclusions: Due to its effectiveness in reducing high EtOH consumption coupled without an effect on water intake, tigecycline was found to be the most promising lead tetracycline compound for further study toward the development of a new pharmacotherapy for the treatment of AUD., (Copyright © 2016 by the Research Society on Alcoholism.)

The suicide bombings in London on 7 July 2005 resulted in a mass casualty situation. Over 50% of casualties were treated at the Royal London Hospital where clinicians witnessed large numbers of severely injured patients. In some casualties human biological foreign material was found embedded in the soft tissue originating from the suicide bombers or other casualties. This had the potential of placing individuals at risk of transmission of blood-borne diseases. Advances in the fields of medicine and biology have led to increased survivorship in the context of trauma and mass casualty incidents. This has resulted in the emergence of ethical scenarios surrounding patient management. A systematic review of the literature of the 7/7 bombings, and suicide bombings reported globally, where biological implantation is noted, was performed to examine the medicolegal issues arising during such attack. Twelve casualties with human tissue implanted were recorded in the 7/7 bombings. While all patients at risk were given prophylaxis based on recommendations by the Health Protection Agency, several ethical considerations surfaced as a result. In this paper, we compare the sequence of events and the management process of the victims of the 7/7 bombings and the evidence-based research regarding blood-borne infection transmission. Furthermore, it explores the ethical dilemmas, experienced by the senior author on 7/7, surrounding prophylaxis for blood-borne diseases and protocols to avoid confusion over best practice in future bombing incidents., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Heterotopic ossification is the formation of bone at extraskeletal sites. The incidence of heterotopic ossification in military amputees from recent operations in Iraq and Afghanistan has been demonstrated to be as high as 65%. Heterotopic ossification poses problems to wound healing, rehabilitation, and prosthetic fitting. This article details the current evidence regarding its etiology, prevention, management, and research strategies.

The Afghanistan conflict has resulted in a large number of service personnel sustaining amputations. Whilst obvious differences exist between military and civilian trauma-related amputations both settings result in life changing injuries. Comparisons offer the potential of advancement and protection of the knowledge gained during the last 12 years. This paper compares the military and civilian trauma-related amputee cohorts' demographics, management and rehabilitation outcomes measures. The UK military Joint Theatre Trauma Registry and a civilian major trauma centre database of trauma-related amputees were analysed. 255 military and 24 civilian amputees were identified. A significant difference (p>0.05) was seen in median age (24, range 18-43, vs. 48, range 24-87 years), mean number of amputations per casualty (1.6±SD 0.678 vs. 1±SD 0.0), mean ISS (22±SD 12.8 vs. 14.7±SD 15.7) and gender (99% males vs. 78%). Rehabilitation outcome measures recorded included the Special Interest Group in Amputee Medicine score where the military group demonstrated significantly better scores (91% Grade E+ compared to 19%). Differences in patients underlying physiology and psychology, the military trauma system and a huge sustained investment in rehabilitation are all contributing factors for these differing outcomes. However the authors also believe that the use of a consultant-led MDT and central rehabilitation have benefited the military cohort in the acute rehabilitation stage and is reflected in the good short-term outcomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Trigger thumb, or stenosing tenovaginitis, is a relatively uncommon condition affecting the flexor pollicis longus tendon of children. The condition is characterized by the formation of a nodule within the tendon and thickening of the tendon sheath as it passes through the flexor pulley of the thumb at the level of the metacarpo-phalangeal joint. The optimum age for surgical intervention continues to be discussed. The aim of this study is to establish the temporal relationship and surgical variables to determine factors that may contribute to recurrence of the condition. A retrospective analysis of the entire surgical logbook and patient notes of a stand-alone consultant paediatric orthopaedic practice was scrutinized. 94 patients, 107 thumbs, over a 13-year period were operated on for trigger thumb. The recurrence rate was found to be 5.61 %. The average age of patients at primary release who went on to recurrence was 2.8 years, which is significantly younger than those that did not recur (p = 0.044). Sensitivity analysis revealed that the primary procedure at an age of less than 2.5 years confers a higher risk of recurrence. The data presented here advocate surgical release of trigger thumb after 2½ years of age, a senior surgeon as lead operator and a transverse skin incision at the level of the nodule or a more extensive "zig-zag" one to clearly see the structures to be released. We recommend that the surgeon ensures the stenosing pulley and sheath are released in their entirety.

Introduction: Terrorists have used the explosive device successfully globally, with their effects extending beyond the resulting injuries. Suicide bombings, in particular, are being increasingly deployed due to the devastating effect of a combination of high lethality and target accuracy. The aim of this study was to identify trends and analyse the demographics and casualty figures of terrorist bombings worldwide., Methods: Analysis of the Global Terrorism Database (GTD) and a PubMed/Embase literature search (keywords "terrorist", and/or "suicide", and/or "bombing") from 1970 to 2014 was performed., Results: 58,095 terrorist explosions worldwide were identified in the GTD. 5.08% were suicide bombings. Incidents per year are increasing (P<0.01). Mean casualty statistics per incidents was 1.14 deaths and 3.45 wounded from non-suicide incidents, and 10.16 and 24.16 from suicide bombings (p<0.05). The kill:wounded ratio was statistically higher in suicide attacks than non-suicide attacks, 1:1.3 and 1:1.24 respectively (p<0.05). The Middle East witnessed the most incidents (26.9%), with Europe (13.2%) ranked 4th. The literature search identified 41 publications reporting 167 incidents of which 3.9% detailed building collapse (BC), 60.8% confined space (CS), 23.5% open space (OS) and 11.8% semi-confined space (SC) attacks. 60.4% reported on suicide terrorist attacks. Overall 32 deaths and 180 injuries per incident were seen, however significantly more deaths occurred in explosions associated with a BC. Comparing OS and CS no difference in the deaths per incident was seen, 14.2(SD±17.828) and 15.63 (SD±10.071) respectively. However OS explosions resulted in significantly more injuries, 192.7 (SD±141.147), compared to CS, 79.20 (SD±59.8). Extremity related wounds were the commonest injuries seen (32%)., Discussion/conclusion: Terrorist bombings continue to be a threat and are increasing particularly in the Middle East. Initial reports, generated immediately at the scene by experienced coordination, on the type of detonation (suicide versus non-suicide), the environment of detonation (confined, open, building collapse) and the number of fatalities, and utilising the Kill:Wounded ratios found in this meta-analysis, can be used to predict the number of casualties and their likely injury profile of survivors to guide the immediate response by the medical services and the workload in the coming days., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The First World War (1914-1918) was the first truly industrial conflict in human history. Never before had rifle fire and artillery barrage been employed on a global scale. It was a conflict that over 4 years would leave over 750,000 British troops dead with a further 1.6 million injured, the majority with orthopaedic injuries. Against this backdrop, the skills of the orthopaedic surgeon were brought to the fore. Many of those techniques and systems form the foundation of modern orthopaedic trauma management. On the centenary of 'the War to end all Wars', we review the significant advances in wound management, fracture treatment, nerve injury and rehabilitation that were developed during that conflict., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

Heterotopic ossification (HO) is the formation of bone at extraskeletal sites. Over 60% of amputees injured by improvised explosive devices in the recent conflict in Afghanistan have developed HO, resulting in functional impairment. It is hypothesised that a key aetiological factor is the blast wave; however, other environmental and medical risk factors, which the casualties have been exposed to, have also been postulated. The suicide terrorist bombings in London in 2005 resulted in many blast-related casualties, many of whom were managed by the Royal London Hospital. This cohort of severely injured patients whose injuries also included trauma-related amputations shared some, but not all, of the risk factors identified in the military population. We reviewed these patients, in particular to assess the presence or absence of military-established risk factors for the formation of HO in these casualties., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Heterotopic ossification (HO) is the formation of mature lamellar bone in extraskeletal soft tissues. It was first described 1000 years ago in the healing of fractures, and in relation to military wounds, texts from the American Civil War and World War I refer to HO specifically. It continues to cause problems to injured service personnel; the consequences of wound and soft tissue complications in traumatic amputations pose particular problems to rehabilitation and prosthetic use. While HO is seen in rare genetic conditions, it is most prevalent after joint replacement surgery and trauma. In the civilian setting HO has been commonly described in patients after traumatic brain injuries, spinal cord injuries and burns. Militarily, as a consequence of recent operations, and the characteristic injury of blast-related amputations, a renewed interest in HO has emerged due to an increased incidence seen in casualties. The heterogeneous nature of a blast related amputation makes it difficult for a single aetiological event to be identified, although it is now accepted that blast, amputation through the zone of injury, increased injury severity and associated brain injuries are significant risk factors in HO formation. The exact cellular event leading to HO has yet to be identified, and as a consequence its prevention is restricted to the use of anti-inflammatory medication and radiation, which is often contraindicated in the acute complex military casualty. A systematic review in PubMed and the Cochrane Database identified research articles related to HO to illustrate the military problem of HO and its management, current research concepts and experimental theories regarding HO. This also served as a gap analysis providing the researchers detail of any knowledge deficit in this field, in particular to the military aspects of HO; 637 out of 7891 articles initially identified that referenced HO were relevant to this review., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Personal protection equipment, improved early medical care, and rapid extraction of the casualty have resulted in more injured service members who served in Afghanistan surviving after severe military trauma. Many of those who survive the initial trauma are faced with complex wounds such as multiple amputations. Although costs of care can be high, they have not been well quantified before. This is required to budget for the needs of the injured beyond their service in the armed forces., Question/purposes: The purposes of this study were (1) to quantify and describe the extent and nature of traumatic amputations of British service personnel from Afghanistan; and (2) to calculate an estimate of the projected long-term cost of this cohort., Methods: A four-stage methodology was used: (1) systematic literature search of previous studies of amputee care cost; (2) retrospective analysis of the UK Joint Theatre Trauma and prosthetic database; (3) Markov economic algorithm for healthcare cost and sensitivity analysis of results; and (4) statistical cost comparison between our cohort and the identified literature., Results: From 2003 to 2014, 265 casualties sustained 416 amputations. The average number of limbs lost per casualty was 1.6. The most common type of amputation was a transfemoral amputation (153 patients); the next most common amputation type was unilateral transtibial (143 patients). Using a Markov model of healthcare economics, it is estimated that the total 40-year cost of the UK Afghanistan lower limb amputee cohort is £288 million (USD 444 million); this figure estimates cost of trauma care, rehabilitation, and prosthetic costs. A sensitivity analysis on our model demonstrated a potential ± 6.19% variation in costs., Conclusions: The conflict in Afghanistan resulted in high numbers of complex injuries. Our findings suggest that a long-term facility to budget for veterans' health care is necessary., Clinical Relevance: Estimates here should be taken as the start of a challenge to develop sustained rehabilitation and recovery funding and provision.

Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites. Reported rates of HO after hip arthroplasty range from 8 to 90 %; however, it is only severe cases that cause problems clinically, such as joint stiffness. The effects of surgical-related controllable intra-operative risk factors for the formation of HO were investigated. Data examined included gender, age of patient, fat depth, length of operation, incision length, prosthetic fixation method, the use of pulsed lavage and canal brush, and component size and material. All cases were performed by the same surgeon using the posterior approach. A total of 510 cases of hip arthroplasty were included, with an overall rate of HO of 10.2 %. Longer-lasting operations resulted in higher grades of HO (p = 0.047). Incisions >10 cm resulted in more widespread HO formation (p = 0.021). No further correlations were seen between HO formation and fat depth, blood loss, instrumentation, fixation methods or prosthesis material. The mini-incision approach is comparable to the standard approach in the aetiology of HO formation, and whilst the rate of HO may not be controllable, a posterior mini-incision approach can limit its extent.

Introduction: Freiberg infraction is a relatively rare osteochondrosis of the metatarsal head. The etiology of Freiberg infraction is poorly understood but likely involves factors such as, repetitive trauma and vascular compromise. When discovered early, Freiberg infraction can be cured with conservative measures but late presentations require surgical intervention. We present a case of stage V Freiberg infraction in a Division I collegiate tennis player that responded to conservative treatment., Case Report: A 20 year old female tennis player presented with worsening of her chronic foot pain. She had tenderness to palpation and diminished range of motion at the second metatarsophalangeal joint. Radiographs revealed late stage Freiberg infraction of the second metatarsal. This patient's pain was successfully treated with conservative measures; prolonging her collegiate tennis career., Conclusion: Surgical intervention is required for definitive treatment of late stage Freiberg infraction. Conservative treatment can be effective in prolonging the athlete's career., Competing Interests: Conflict of Interest: Nil

Background and Objectives: Miscommunication during patient hand-off in the inpatient setting can lead to serious medical errors. Previous studies indicate heterogeneity in handoff practices among physicians in training. We sought to determine current practice patterns of patient hand-offs in family medicine residencies and training methods to reinforce effective transfer of care., Methods: We developed 13 questions relating to patient hand-offs that were included in the Spring 2014 CERA Family Medicine Program Directors Survey. Descriptive statistics were generated for each survey item., Results: We received 224 survey responses (response rate of 50%). The typical inpatient was subject to an average of seven transfers of care from a Thursday morning to a Monday morning. Use of two strategies consistent with best practices (face-to-face hand-off, use of a dedicated area) was very high. There was wide variation in training methods for patient transfer and infrequent use of national resources. Half of all residency programs relied on supervision as the primary method of instruction in patient hand-off. Estimated patient safety events in the last year attributed to a breakdown in hand-off procedure occurred "rarely/never" in 73% of programs., Conclusions: The vast majority of family medicine residencies use at least two of three best practices in patient hand-offs, though there was wider variation in the processes of hand-offs. Frequent hand-offs associated with a night float system is a potential cause of increased errors, though we were unable to measure actual patient safety events.

The ever-increasing production and use of nanocrystaline semiconductors (Quantum dots; QDs) will inevitably result in increased appearance of these nanomaterials in the aquatic environment. However, the behavior and potential toxicity of heavy metal constituted nanoparticulates in aquatic invertebrates is largely unknown, especially with regard to molecular responses. The freshwater crustacean Daphnia pulex is a well-suited toxicological and ecological model to study molecular responses to environmental stressors. In this study, D. pulex were exposed for 48 h to sublethal doses of QDs (25% and 50% of LC50) with differing spectral properties (CdTe and CdSe/ZnS QDs) and Cd and Zn salts. Our data suggest that acute exposure to both CdSO4 and Cd-based QDs leads to Cd uptake in vivo, which was biologically supported by the observation of increased expression of metallothionein (MT-1). Furthermore, Cd, Zn, and CdSe/ZnS QDs induced different patterns of gene expression regarding stress defense and DNA repair, which furthers our knowledge regarding which response pathways are affected by nanoparticulate forms of metals versus ionic forms in aquatic crustaceans., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The principal feature of injuries from World War 1 was musculoskeletal trauma and injury to peripheral nerves as a result of damage to the upper and lower limbs caused by gunshot wounds and fragments of artillery munitions. Amputation was used as a treatment in field hospitals to save lives; limb conservation was a secondary consideration. A century later, the principal feature of injuries to soldiers in today's wars in Iraq and Afghanistan is also musculoskeletal trauma and injury to the peripheral nerves caused by improvised explosive devices. Common to both types of injury is postamputation pain. We searched The Lancet's archives in this Series paper to show the efforts of surgeons in World War 1 to understand and treat postamputation pain in its own right both during and immediately after the war. Despite unprecedented patient numbers and levels of civilian medical expertise, little progress was made in providing relief from this type of pain, a grave concern to the surgeons treating these soldiers. Today postamputation pain is understood beyond a surgical context but remains a complex and poorly understood condition with few effective treatments., (Copyright © 2014 Elsevier Ltd. All rights reserved.)