Dark Matter Annihilation inside Large-Volume Neutrino Detectors.

New particles in theories beyond the standard model can manifest as stable relics that interact strongly with visible matter and make up a small fraction of the total dark matter abundance. Such particles represent an interesting physics target since they can evade existing bounds from direct detection due to their rapid thermalization in high-density environments. In this work we point out that their annihilation to visible matter inside large-volume neutrino telescopes can provide a new way to constrain or discover such particles. The signal is the most pronounced for relic masses in the GeV range, and can be efficiently constrained by existing Super-Kamiokande searches for dinucleon annihilation. We also provide an explicit realization of this scenario in the form of secluded dark matter coupled to a dark photon, and we show that the present method implies novel and stringent bounds on the model that are complementary to direct constraints from beam dumps, colliders, and direct detection experiments.

Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series.

The prevalence of mental health disorders is high among people with Cystic Fibrosis. The psychological symptoms in CF are associated with poor adherence, worse treatment outcomes, and greater health utilization/cost. Mental health and neurocognitive Adverse Events (AEs) have been reported with all available Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in small groups of patients. We report our experience with a dose reduction strategy in 10 of our patients on elexacaftor/tezacaftor/ivacaftor (7.9% of total number of patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or mental slowness after initiation of full dose treatment. Standard dose elexacaftor/tezacaftor/ivacaftor resulted in 14.3 points improvement in mean Percent Predicted Forced Expiratory Volume in 1 s (ppFEV1), and a mean difference in sweat chloride of -39.3 mmol/L. We initially discontinued and/or reduced therapy according to the AEs severity, with a subsequent planned dose escalation every 4-6 weeks guided by sustainability of clinical effectiveness, absence of AEs recurrence, and patients' preferences. Clinical parameters including lung function and sweat chloride were monitored for up to 12 weeks to assess ongoing clinical response to the reduced dose regimen. Dose reduction resulted in resolution of self-reported mental/psychological AEs, without loss of clinical effectiveness (ppFEV1 was 80.7% on standard dose, and 83.4% at 12 weeks on reduced dose; sweat chloride was 33.4 and 34 mmol/L on standard and reduced dose, respectively). Furthermore, in a subgroup of patients who completed 24 weeks of the reduced dose regimen, repeat low dose Computed Tomography imaging showed a significant response when compared to pre-initiation of elexacaftor/tezacaftor/ivacaftor.

Definitions of serious injury in long-term residential care: a systematic review protocol.

Background: Evidence indicates that the reporting of serious injury in long-term residential care has increased substantially over the past decade. However, what constitutes a serious injury in residential care is poorly and inconsistently defined. This may result in incidences being unnecessarily reported as a serious injury. It is therefore, crucial to develop a consistent definition of serious injury to reduce reporting burden and to facilitate comparison between different residential care settings and across jurisdictions. This protocol describes the methods for a systematic review of existing definitions from the literature to inform the development of a consistent definition of serious injury in long-term residential care. Methods: A wide range of published peer-reviewed and grey literature will be sought for this review, including guidance and policy documents. Searches will be conducted of databases including MEDLINE, CINAHL, SocINDEX, Academic Search Ultimate, and Westlaw International. Grey literature database searches will include Trip and Social Care Online. Country specific searches of government and health and social care websites will be conducted. Quality appraisal will be facilitated using the Quality Assessment for Diverse Studies (QuADS) tool and Tyndall's checklist. The level of confidence in the findings will be assessed using the GRADE CERQual approach. A customised data extraction form will be used to extract data to reduce the risk of bias. Conceptual content analysis of data will facilitate identification of definitions of serious injury and their frequency within texts. Conclusions: The findings will inform the development of a consistent definition of serious injury in long-term residential care that will reduce reporting burden, facilitate the accuracy of data collected and allow for comparison across jurisdictions. A more universal and consistent definition will enable regulators, policy makers, service providers and researchers to develop policy and practical interventions to prevent the occurrence of serious injury in long-term residential care.

Posterior (Boyd) approach to terrible triad injuries.

BACKGROUND: A 'terrible triad injury of the elbow' (TTIE) refers to an injury pattern involving posterior dislocation of the ulnohumeral joint, fracture of the radial head, and fracture of the coronoid process of the ulna. It is a complex injury to the elbow joint and can result in long-term elbow instability, pain, stiffness, and arthritis. In specific cases, it may be treated conservatively, but in most circumstances, surgical stabilization is advised.The 'drop sign' is an objective static radiographically measured ulnohumeral distance of ≥4 mm seen intraoperatively and postoperatively. Although controversial, it may portend postoperative instability and arthritis. The senior author repairs these injuries in a standardized fashion through a modified Boyd rather than a lateral approach. Our aim was to assess the number of cases demonstrating an intraoperative drop sign after surgical treatment of a TTIE with this approach. METHODS: We retrospectively analyzed 22 consecutive patients with 23 acute TTIEs. These injuries were treated by a single surgeon using a modified Boyd (posterior) approach to the elbow. Intraoperative image intensifier x-rays were analyzed by the two authors to assess for a 'drop sign'. RESULTS: None of the 23 cases had 'drop signs' on intraoperative imaging after stabilization. No patient has redislocated, underwent reoperation, or had symptoms of instability at follow-up. CONCLUSION: None of our patient cohort had an intraoperative 'drop sign' after standardized stabilization for a TTIE injury using a modified Boyd approach.

Repair of sternoclavicular joint ligament: a novel approach.

BACKGROUND: Posterior sternoclavicular dislocations are common in younger patients and are frequently due to high energy sporting incidents. AIM: We aim to demonstrate a novel technique that is safe and aims to provide good functional post-operative outcomes for patients with this injury. METHODS: This was a single-surgeon case series of four young patients from October 2017 to July 2019. The operative technique involved relocating the joint and holding it in situ with nylon suture tape. The tape was anchored in holes drilled in the sternum and passed through tunnels drilled into the medial clavicle. All of the patients were contacted retrospectively and a Nottingham Clavicle Score (NCS) was performed for each patient on a post-operative basis. RESULTS: No intra-operative or post-operative complications were noted. All of the patients demonstrated a significant improvement in their functional outcomes after the operation. The average NCS for the four patients was 82/100. DISCUSSION: There are a variety of techniques described in the literature to repair this ligament using either plates or tendon grafts. All of these techniques describe the drilling of anteroposterior holes in the manubrium and clavicle which run the intra-operative risk of perforating a major vessel. This paper is the first one to describe a technique which uses superior inferior holes which minimizes the risks, making the procedure safer for the patient. CONCLUSIONS: We believe this novel technique is safer than the existing described techniques, and it does not compromise on functional outcomes.

CT versus MRI planning for reverse geometry total shoulder arthroplasty.

INTRODUCTION: Preoperative planning for Reverse Total Shoulder Arthroplasty (RTSA) using CT or MRI is well described.1, 2, 3, 4, 5, 6, 7 We aimed to compare pre-operative CT versus MRI measurement accuracy for predicting intra-operative glenoid implant sizing. METHODS: All patients with a preoperative CT or MRI undergoing RTSA at our tertiary referral center from October 2017 to February 2020 were included. Data was collected from theatre and implant registers. Glenosphere Width (GW) and Baseplate Central Screw Length (BCSL) were independently predicted from pre-operative CT or MRI imaging by 2 blinded senior authors. A sub-group analysis was also performed between trauma and non-trauma CT cases. SPSS v26 was used for statistical comparison between predicted and actual implants. RESULTS: 71 data sets from 69 patients were included for analysis: 31 CT predictions and 40 MRI predictions. 61.3% of CT measured GW predictions were accurate compared to 82.5% of MRI predictions (p = 0.045). BCSL predictions were 77.4% and 70% accurate for CT and MRI respectively, without significant difference. There was no significant difference in sub-group analysis for trauma vs elective CT accuracy of BCSL or GW measurements. CONCLUSION: MRI imaging may be superior to CT for predicting GW and no less accurate than CT for predicting BCSL in the elective setting. No difference in CT measurement accuracy was seen between trauma and elective settings. While simultaneously clearly defining shoulder soft tissue anatomy, MRI may also be the preferred modality for bony measurements during pre-operative planning for elective RTSA.

Incidence of avascular necrosis following biceps tenodesis during proximal humerus open reduction and internal fixation.

Avascular necrosis (AVN) may occur in up to 77% of proximal humeral fractures and can cause fixation failure. Risk factors include fracture position, calcar length and medial hinge integrity. We routinely perform intra-articular biceps tenotomy with tenodesis at the level of pectoralis major to facilitate fragment identification and potentially ameliorate post-operative pain relief. Concern exists that tenotomising the biceps damages the adjacent arcuate artery, potentially increasing the rate of AVN. The purpose of this study was to evaluate whether biceps tenodesis is associated with an increased risk of radiographically evident humeral head AVN. 61 fractures surgically treated over a 52-month period were retrospectively reviewed and radiographically assessed in accordance with Neer's classification, calcar-length and medial hinge integrity. 40, 20 and 1 were four-, three- and two-part fractures respectively. 37 had a calcar-length less than 8mm and 26 suffered loss of the medial hinge. The median radiographic follow-up was 23 months. There was radiographic evidence of humeral head AVN in only one case, comparing favourably to rates quoted in current literature. In our experience, intra-articular biceps tenotomy with the deltopectoral approach was thus not associated with a significantly increased risk of humeral head AVN, even in complex four-part fractures.

Determining the accurate placement of a posterior portal in shoulder arthroscopy with the use of computerized tomography images.

Background: Portal placement is an important factor in performing a successful shoulder arthroscopy. Recent cadaveric studies have found variance in the anatomy of the glenohumeral joint. Our aim was to determine if computerized tomography (CT) images could be used to map the trajectory of the posterior portal objectively and then measure the distance between this trajectory and palpable landmarks to apply this knowledge to clinical practice. Methods: Two-dimensional multiplanar reformatted CT images were generated using OsiriX (Pixmeo, Switzerland) from CT images performed in a tertiary hospital over a 1-month period. The center of the glenoid was identified and a trajectory through it radiologically mapped. Horizontal and lateral measurements were taken from this trajectory to both the posterolateral edge of the acromion and tip of the coracoid. Results: Following application of inclusion and exclusion criteria, 226 shoulders were analyzed. Fifty scans were selected at random and re-reviewed by the primary examiner to assess intra-rater reliability which showed strong correlation and no significant differences between first and second measurements (P < .01, r > 0.6). The mean distance from acromion to portal trajectory was 1.39 cm inferiorly (95% confidence interval [CI] 1.31-1.48, standard deviation [SD] 0.65 cm) and 1.44 cm medially (95% CI 1.35-1.53, SD 0.71 cm). The mean distance from the coracoid to the trajectory was 1.71 cm inferiorly (95% CI 1.64-1.78, SD 0.55 cm) and 1.26 cm medially (95% CI 1-2-1.31, SD 0.45 cm). Paired t-test analysis between right and left shoulders within the same subject, where these data were available (n = 81), showed no significant difference (P > .05) between sides. Subset analysis was also performed between males and females, but only showed a significant difference between the vertical distance from the coracoid process to the center of the glenohumeral joint. This distance was shorter in females compared to males (1.56 cm in females compared to 1.84 cm in males, P < .001). Conclusions: Knowledge of shoulder anatomy is vital to the placement of arthroscopic portals, yet research on this topic has been based primarily on surface anatomy, small sample sized cadaveric studies or expert opinion alone. Our study shows that posterior portal placement in shoulder arthroscopy can be measured objectively using CT scanning.

Gravitational Wave Bursts as Harbingers of Cosmic Strings Diluted by Inflation.

A standard expectation of primordial cosmological inflation is that it dilutes all relics created before its onset to unobservable levels. We present a counterexample to this expectation by demonstrating that a network of cosmic strings diluted by inflation can regrow to a level that is potentially observable today in gravitational waves (GWs). In contrast to undiluted cosmic strings, whose primary GW signals are typically in the form of a stochastic GW background, the leading signal from a diluted cosmic string network can be distinctive bursts of GWs within the sensitivity reach of current and future GW observatories.

Harvesting 48V at the National Superconducting Cyclotron Laboratory.

As part of an effort to develop aqueous isotope harvesting techniques at radioactive beam facilities, 48V and a cocktail of primary- and secondary-beam ions created by the fragmentation reaction of a 160 MeV/nucleon 58Ni beam were stopped in an aqueous target cell. After collection, 48V was separated from the mixture of beam ions using cation-exchange chromatography. The extraction efficiency from the aqueous solution was (47.0 ± 2.5)%, and the isolated 48V had a radiochemical purity of 95.8%. This proof-of-concept work shows that aqueous isotope harvesting could provide significant quantities of rare isotopes which are currently unavailable at conventional facilities.

A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing.

The development of clinically viable delivery methods presents one of the greatest challenges in the therapeutic application of CRISPR/Cas9 mediated genome editing. Here, we report the development of a lipid nanoparticle (LNP)-mediated delivery system that, with a single administration, enabled significant editing of the mouse transthyretin (Ttr) gene in the liver, with a >97% reduction in serum protein levels that persisted for at least 12 months. These results were achieved with an LNP delivery system that was biodegradable and well tolerated. The LNP delivery system was combined with a sgRNA having a chemical modification pattern that was important for high levels of in vivo activity. The formulation was similarly effective in a rat model. Our work demonstrates that this LNP system can deliver CRISPR/Cas9 components to achieve clinically relevant levels of in vivo genome editing with a concomitant reduction of TTR serum protein, highlighting the potential of this system as an effective genome editing platform.

Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo.

Small interfering RNA (siRNA)-based drugs require chemical modifications or formulation to promote stability, minimize innate immunity, and enable delivery to target tissues. Partially modified siRNAs (up to 70% of the nucleotides) provide significant stabilization in vitro and are commercially available; thus are commonly used to evaluate efficacy of bio-conjugates for in vivo delivery. In contrast, most clinically-advanced non-formulated compounds, using conjugation as a delivery strategy, are fully chemically modified (100% of nucleotides). Here, we compare partially and fully chemically modified siRNAs in conjugate mediated delivery. We show that fully modified siRNAs are retained at 100x greater levels in various tissues, independently of the nature of the conjugate or siRNA sequence, and support productive mRNA silencing. Thus, fully chemically stabilized siRNAs may provide a better platform to identify novel moieties (peptides, aptamers, small molecules) for targeted RNAi delivery.

A case of traumatic infraorbital neuroma.

A 53-year-old Afghan man presented with a 12-month history of left proptosis, diplopia and facial swelling 20 years after a bomb blast injury. Magnetic resonance and computed tomography imaging revealed a well-circumscribed lesion centred within the left inferior orbit/superior maxillary sinus along with left orbital fracture. Histopathology and immunostaining of the debulked lesion were consistent with traumatic neuroma of the infraorbital nerve. Infraorbital neuromas have developed following orbital decompression surgeries but have not been reported previously following non-surgical trauma.

Arthroscopic Sternoclavicular Joint Diskectomy for Acute and Chronic Tears.

PURPOSE: To describe the results and functional scores in a group of patients who underwent arthroscopic excision of a symptomatic sternoclavicular joint (SCJ) disk tear with a minimum follow-up period of 2 years. METHODS: Between April 2010 and December 2014, 14 patients underwent arthroscopic excision of a torn SCJ disk. Patients whose intended surgery was an isolated diskectomy and underwent that surgery only, with no additional procedure, were included. The minimum follow-up period was 24 months. All patients underwent an arthroscopic SCJ diskectomy. Postoperatively, no immobilization was required, and the patients were encouraged to mobilize as pain permitted. The patients were assessed preoperatively and at final follow-up with the visual analog scale score for pain, Rockwood score, and QuickDASH (short version of the Disabilities of the Arm, Shoulder and Hand questionnaire) score. RESULTS: The average age at surgery was 29.4 years (range, 19-39 years). Ten of the patients had been symptom free before a specific incident, after which SCJ symptoms developed. The other 4 patients reported a gradual onset of symptoms and were considered to have chronic tears. The average duration of symptoms was 22.8 months (range, 6-48 months). At a mean follow-up of 33.4 months (range, 24-59 months), a significant improvement in the Rockwood score was noted, from 7 (range, 5-9; standard deviation [SD], 1.4) to 13.6 (range, 9-15; SD, 1.9) (P = .001) (minimal clinically important difference not described). The mean QuickDASH score improved from 23.7 points (range, 6.8-40.9 points; SD, 11.8 points) to 8 points (range, 0-29.5 points; SD, 9 points) (P = .0024) (minimal clinically important difference, 13.4 points). There were no reported complications and specifically no instability. CONCLUSIONS: The results of this series suggest that arthroscopic SCJ diskectomy is a safe and reproducible procedure for the treatment of patients with symptomatic SCJ disk tears. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Arthroscopic Intra-articular Disk Excision of the Sternoclavicular Joint.

The sternoclavicular joint (SCJ) has a complete intra-articular disk that can be damaged either as a result of trauma or as part of ongoing degenerative joint disease. Although often asymptomatic, SCJ disk tears may lead to mechanical symptoms and pain. Previously, isolated symptomatic SCJ disk tears have only occasionally been mentioned in the literature with a few associated case reports of diskectomy by open arthrotomy. With improved imaging and availability of magnetic resonance imaging scans and the advent of SCJ arthroscopy it is now possible to treat symptomatic SCJ disk tears by arthroscopic excision. In this Technical Note, we describe the diagnosis of a torn SCJ disk and the technique of arthroscopic excision of a torn SCJ disk.

Sternoclavicular joint osteophytosis: a difficult diagnosis to swallow.

Unexplained dysphagia requires prompt investigation to rule out a possible underlying malignancy. We describe the case of a 60-year-old man who presented to his family practitioner with a 1-year history of increasing dysphagia with associated pain over the front of his chest. He was referred on to an ear, nose and throat specialist where no obvious laryngeal pathology was found at direct laryngoscopy, but an 'indentation' of the right anterior larynx, which increased with external pressure on the sternoclavicular joint (SCJ), was noted. A subsequent CT scan of his neck demonstrated osteoarthritis of the right SCJ with an abnormally large posterior osteophyte. The patient was subsequently referred on to an orthopaedic surgeon specialising in SCJ surgery and underwent an arthroscopic excision of his right SCJ. Soon after surgery, the patient's dysphagia had settled and his symptoms remain resolved 1 year post surgery.

Biofabrication of soft tissue templates for engineering the bone-ligament interface.

Regenerating damaged tissue interfaces remains a significant clinical challenge, requiring recapitulation of the structure, composition, and function of the native enthesis. In the ligament-to-bone interface, this region transitions from ligament to fibrocartilage, to calcified cartilage and then to bone. This gradation in tissue types facilitates the transfer of load between soft and hard structures while minimizing stress concentrations at the interface. Previous attempts to engineer the ligament-bone interface have utilized various scaffold materials with an array of various cell types and/or biological cues. The primary goal of this study was to engineer a multiphased construct mimicking the ligament-bone interface by driving differentiation of a single population of mesenchymal stem cells (MSCs), seeded within blended fibrin-alginate hydrogels, down an endochondral, fibrocartilaginous, or ligamentous pathway through spatial presentation of growth factors along the length of the construct within a custom-developed, dual-chamber culture system. MSCs within these engineered constructs demonstrated spatially distinct regions of differentiation, adopting either a cartilaginous or ligamentous phenotype depending on their local environment. Furthermore, there was also evidence of spatially defined progression toward an endochondral phenotype when chondrogenically primed MSCs within this construct were additionally exposed to hypertrophic cues. The study demonstrates the feasibility of engineering spatially complex soft tissues within a single MSC laden hydrogel through the defined presentation of biochemical cues. This novel approach represents a new strategy for engineering the ligament-bone interface. Biotechnol. Bioeng. 2017;114: 2400-2411. © 2017 Wiley Periodicals, Inc.

Locking plate external fixation and negative pressure wound therapy for treatment of a primary infection in a closed clavicle fracture.

Infection in a clavicle fracture is uncommon, but remains a challenging problem. A paucity of soft tissue coverage often combined with significant displacement and interfragmentary movement add complexity to an already difficult situation for effective infection treatment. External fixation in principle offers a means of achieving fracture stability, while the infection is being eradicated. We present the case of a closed clavicle fracture, initially treated conservatively, that presented 5 weeks later with infection. The fracture was definitively treated with external fixation using a locking plate positioned superficially to the skin, plus negative pressure wound therapy and subsequent secondary closure and antibiotic therapy. This case illustrates a novel method of treatment in this unusual presentation that was well tolerated by the patient and resulted in a good clinical outcome.

All patients deserve holistic care.

Towards the end of my first year of training, I was on placement on a hospital ward when I heard the alarm bell go off in a bathroom.