Multi-GeV Electron Acceleration in Wakefields Strongly Driven by Oversized Laser Spots.

Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250 TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies E_{max}>2.5 GeV, in fields exceeding 500 GV m^{-1}, with more than 80 pC of charge at energies E>1 GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.

The Outreach Virtual Fracture Clinic - a Pilot Report of the Initial Nine Months.

The virtual fracture clinic (VFC) enables the safe, cost-effective delivery of high-quality patient-centred fracture care, whilst reducing hospital footfall. Within our institution, an Outreach VFC was launched, accepting a pre-defined range of trauma referrals from the outreach centre's emergency department (ED). The initial nine months' worth of cases referred to the Outreach VFC were assessed. The injury pattern, time to review, treatment plan and discharge destination of each referred patient were examined. A total of 822 patients were referred to the Outreach VFC during its initial nine months in operation. Owing to COVID-19-related alterations in the patient pathway, 58.1% of patients were referred on to fracture clinic/ED, with 34.4% of patients being referred for physiotherapy input. 44.9% of patients were reviewed at the Outreach VFC within 72 hours of ED presentation, with 88.6% of patients reviewed within 7 days. The Outreach VFC pilot initiative saved the Dublin Midlands Hospitals Group approximately €83,022 over nine months. The Outreach VFC model represents a novel approach to trauma care delivery with advantages for patient and hospital alike. Rural communities serve to benefit from its future implementation and the remote management of orthopaedic trauma. The Outreach VFC model provides a means of delivering safe and timely orthopaedic care whilst maintaining high levels of patient satisfaction.

National Hip Fracture Incidence - Past, Present and Future Projections.

Aims Hip fractures are a significant source of morbidity and mortality, with occurrences set to increase as our population continues to age. The aim of this study is to determine the current and future incidence of hip fractures in Ireland based on predicted population growth. Methods A search was performed of the Irish Hip Fracture Database to identify all hip fracture patients, aged over 60, from 2017-2019. Data on the current population, as well as projections up to 2046, were obtained from the Central Statistics Office, so as to determine projected hip fracture incidence in the coming decades. Results The incidence of hip fractures, in the Irish population aged over 60, was an average of 389.3 per 100,000 from 2017-2019. Annual hip fracture numbers are expected to increase by at least 158.8% by 2046, assuming a stable incidence rate. Conclusion The age and gender specific incidence of hip fractures in Ireland in those over 60 has remained stable compared to previous years. However, this study projects there will be a significant increase in hip fractures in Ireland in the coming decades and there will need to be appropriate resource allocation within future healthcare budgets.

Tape strips in dermatology research.

Tape strips have been used widely in dermatology research as a minimally invasive method to sample the epidermis, avoiding the need for skin biopsies. Most research has focused on epidermal pathology, such as atopic eczema, but there is increasing research into the use of tape strips in other dermatoses, such as skin cancer, and the microbiome. This review summarizes the technique of tape stripping, and discusses which dermatoses have been studied by tape stripping and alternative minimally invasive sampling methods. We review the number of tape strips needed from each patient and the components of the epidermis that can be obtained by tape stripping. With a focus on protein and RNA extraction, we address the techniques used to process tape strips. There is no optimal protocol to extract protein, as this depends on the abundance of the protein studied, its level of expression in the epidermis and its solubility. Many variables can alter the amount of protein obtained from tape strips, which must be standardized to ensure consistency between samples. No study has compared different RNA extraction techniques, but our own experience is that RNA yield is optimized by using 20 tape strips and the use of a cell scraper.

New Light on the Mechanism of Phototransduction in Phototropin.

Phototropins are photoreceptor proteins that regulate blue light-dependent biological processes for efficient photosynthesis in plants and algae. The proteins consist of a photosensory domain that responds to the ambient light and an output module that triggers cellular responses. The photosensory domain of phototropin from Chlamydomonas reinhardtii contains two conserved LOV (light-oxygen-voltage) domains with flavin chromophores. Blue light triggers the formation of a covalent cysteine-flavin adduct and upregulates the phototropin kinase activity. Little is known about the structural mechanism that leads to kinase activation and how the two LOV domains contribute to this. Here, we investigate the role of the LOV1 domain from C. reinhardtii phototropin by characterizing the structural changes occurring after blue light illumination with nano- to millisecond time-resolved X-ray solution scattering. By structurally fitting the data with atomic models generated by molecular dynamics simulations, we find that adduct formation induces a rearrangement of the hydrogen bond network from the buried chromophore to the protein surface. In particular, the change in conformation and the associated hydrogen bonding of the conserved glutamine 120 induce a global movement of the ß-sheet, ultimately driving a change in the electrostatic potential on the protein surface. On the basis of the change in the electrostatics, we propose a structural model of how LOV1 and LOV2 domains interact and regulate the full-length phototropin from C. reinhardtii. This provides a rationale for how LOV photosensor proteins function and contributes to the optimal design of optogenetic tools based on LOV domains.

Auto-Decompression - Preserved Neurological Function in Bilateral Cervical Facet Dislocations

Introduction Bilateral cervical facet dislocation (BCFD) is an uncommon injury with a high incidence of severe neurological impairment. We describe 4 cases of BCFD with preserved neurological function. Cases Case 1: A 78-year-old female who suffered two ground level falls (GLFs). Pre-operative American Spinal Injury Association (ASIA) Score was C5D. Imaging revealed a BCFD at C6/C7 and a C6 laminar fracture. Case 2: A 63-year-old male suffered a fall down 14 steps. Pre-operative ASIA score was E. Imaging demonstrated a BCFD at C7/T1, and a C6 laminar fracture. Case 3: A 46-year-old male collided with a tree while descending a hill on a bicycle. Pre-operative ASIA score was C6D. Imaging revealed a BCFD at C7/T1 and a C7 laminar fracture. Case 4: A 67-year-old male suffered a GLF while exiting a stationary car. Pre-operative ASIA score on admission was E. Imaging revealed a BCFD at C6/C7 with bilateral laminar fractures at C5 and C6. Outcome All cases underwent 2-stage surgical fixation. All cases maintained or had an improved ASIA score post-operatively. Conclusion In all cases, the presence of concurrent laminar fractures resulted in an auto-decompression of the spinal canal, preserving neurological function.

Habitual condom use across partner type and sexual position among younger gay and bisexual men: findings from New Zealand HIV behavioural surveillance 2006-2011.

OBJECTIVES: Our objectives were to investigate demographic and behavioural factors associated with condom use and to examine how habitual condom use was across partner types and sexual positions among younger men who have sex with men (YMSM), aged 16-29, surveyed in New Zealand. METHODS: We analysed the 2006-2011 national HIV behavioural surveillance data from YMSM who reported anal intercourse in four scenarios of partner type and sexual position: casual insertive, casual receptive, regular insertive and regular receptive. For each, respondents' condom use was classified as frequent (always/almost always) or otherwise, with associated factors identified with multivariate mixed-effect logistic regression. Habitual condom use across scenarios was examined using a latent variable technique that estimated the intraclass correlation coefficient (ICC). RESULTS: Frequent condom use was reported for 63.6% of 5153 scenarios reported from 2412 YMSM. Frequent use increased from boyfriend to fuckbuddy to casual partners. Infrequent use was associated with online recruitment, Pacific ethnicity, less education, HIV positivity, sex with women, having ≥20 sexual partners versus 1 and reporting insertive and receptive sexual positions. Frequent condom use was associated with having two to five sexual partners versus one and shorter regular partnerships. The ICC=0.865 indicated highly habitual patterns of use; habitual infrequent condom use was most prevalent with regular partners (53.3%) and habitual frequent condom use was most prevalent with casual partners (70.2%) and for either sexual position (50.5% and 49.1%). CONCLUSIONS: Habitual condom use among YMSM highlights the value of early, engaging and sustained condom promotion. Public health should provide better and more compelling condom education, training and promotion for YMSM.

Limits on the spin-dependent WIMP-nucleon cross sections from the first science run of the ZEPLIN-III experiment.

We present new experimental constraints on the WIMP-nucleon spin-dependent elastic cross sections using data from the first science run of ZEPLIN-III, a two-phase xenon experiment searching for galactic dark matter weakly interacting massive particles based at the Boulby mine. Analysis of approximately 450 kg x days fiducial exposure allow us to place a 90%-confidence upper limit on the pure WIMP-neutron cross section of sigma(n)=1.9x10(-2) pb at 55 GeV/c(2) WIMP mass. Recent calculations of the nuclear spin structure based on the Bonn charge-dependent nucleon-nucleon potential were used for the odd-neutron isotopes 129Xe and 131Xe. These indicate that the sensitivity of xenon targets to the spin-dependent WIMP-proton interaction could be much lower than implied by previous calculations, whereas the WIMP-neutron sensitivity is impaired only by a factor of approximately 2.

Rotational drift of mandibular third molar teeth: a series of four cases.

Rotational drift of mandibular third molar teeth is a challenge for clinicians to predict and manage. Evidence on the incidence and degree of rotation is sparse. As the factors influencing rotation are not defined, prediction is impossible. A series of four cases with lower third molar rotation are presented and discussed. Significant rotation can alter the degree of difficulty for an extraction. A lack of well-documented cases has hindered investigation of this phenomenon. Further research is required to identify the aetiology, incidence and increase in risk factors caused by such rotational drift.

Timing in the absence of supraspinal input I: variable, but not fixed, spaced stimulation of the sciatic nerve undermines spinally-mediated instrumental learning.

Rats with complete spinal transections are capable of acquiring a simple instrumentally trained response. If rats receive shock to one hind limb when the limb is extended (controllable shock), the spinal cord will learn to hold the leg in a flexed position that minimizes shock exposure. If shock is delivered irrespective of leg position, subjects do not exhibit an increase in flexion duration and subsequently fail to learn when tested with controllable shock (learning deficit). Just 6 min of variable intermittent shock produces a learning deficit that lasts 24 h. Evidence suggests that the neural mechanisms underlying the learning deficit may be related to those involved in other instances of spinal plasticity (e.g. windup, long-term potentiation). The present paper begins to explore these relations by demonstrating that direct stimulation of the sciatic nerve also impairs instrumental learning. Six minutes of electrical stimulation (mono- or biphasic direct current [DC]) of the sciatic nerve in spinally transected rats produced a voltage-dependent learning deficit that persisted for 24 h (experiments 1-2) and was dependent on C-fiber activation (experiment 7). Exposure to continuous stimulation did not produce a deficit, but intermittent burst or single pulse (as short as 0.1 ms) stimulation (delivered at a frequency of 0.5 Hz) did, irrespective of the pattern (fixed or variable) of stimulus delivery (experiments 3-6, 8). When the duration of stimulation was extended from 6 to 30 min, a surprising result emerged; shocks applied in a random (variable) fashion impaired subsequent learning whereas shocks given in a regular pattern (fixed spacing) did not (experiments 9-10). The results imply that spinal neurons are sensitive to temporal relations and that stimulation at regular intervals can have a restorative effect.

Successful control of an outbreak of invasive aspergillosis in a regional haematology unit during hospital construction works.

We report the successful control of an outbreak of six cases of nosocomial invasive aspergillosis (IA) in our haematology unit coinciding with major hospital construction works. Infection control changes included unit relocation, impermeable barriers at construction site, face-masking and voriconazole prophylaxis of 18 further high-risk patients, none of which developed breakthrough IA. A multi-faceted pre-emptive approach involving clinicians, hospital management, engineering and building departments is essential in preventing nosocomial IA outbreaks.

ASC acts in a caspase-1-independent manner to worsen acute pneumonia caused by Pseudomonas aeruginosa.

PURPOSE: Pseudomonas aeruginosa expresses a type III secretion system (T3SS) that activates the host inflammasome-mediated immune response. We examined the role of inflammasome activation in severe infection outcomes. METHODS: We infected C57BL/6 (B6) mice lacking inflammasome components ASC or caspase-1/11 with a highly virulent strain of P. aeruginosa, PSE9, using a mouse model of pneumonia. We evaluated inflammasome activation in vitro by infecting bone marrow-derived macrophages (BMDMs) with PSE9 and measuring cell death and release of inflammasome-dependent cytokines IL-18 and IL-1ß. A bioluminescent reporter assay was used to detect activity of caspase-1 and caspase-3/7 in BMDMs from B6 and ASC-deficient mice.Results/Key Findings. ASC-/- mice exhibited significantly improved survival relative to caspase-1/11-/- mice and B6 mice, demonstrating that ASC and caspase-1/11 play differential roles in P. aeruginosa infection. We found that ASC-/- BMDMs exhibited significantly reduced cell death relative to B6 BMDMs, while caspase-1/11-/- BMDMs were resistant to cell death. IL-18 and IL-1ß were both detected from supernatants of infected B6 BMDMs, but cytokine release was abrogated in both ASC-/- and caspase-1/11-/- BMDMs. We detected a 2.5-fold increase in the activation of caspase-3/7 in PSE9-infected B6 BMDMs, but no increase in infected ASC-/- BMDMs. Cell death, cytokine release and caspase-3/7 activity were dependent on a functional T3SS. CONCLUSIONS: Collectively, these results are consistent with a model whereby the T3SS apparatus of P. aeruginosa activates the caspase-1-dependent inflammasome and caspase-3/7 through an ASC-dependent mechanism. This activation may have implications for the outcomes of P. aeruginosa infections.

Detection and subcellular localization of an AML1 chimeric protein in the t(8;21) positive acute myeloid leukemia.

AML1, a gene encoding a protein of the PEBP2/CBF family of transcription factors is disrupted by translocations associated with human leukemia. In the t(8;21) acute myelogenous leukemia (AML), AML1 was found fused to a gene on chromosome 8 that we designated CDR (also known as ETO and MTG8). Immunoprecipitation experiments followed by immunoblotting using a combination of antibodies against different epitopes of one of the predicted chimeric proteins encoded by a fully characterized fusion transcript enabled us to visualize a chimeric protein in the t(8;21) Kasumi-1 cell line. The estimated size of this protein is 64 kDa. Immunoblotting of leukemic blasts containing the t(8;21) detected a protein of the same size. Immunofluorescence experiments indicate that the chimeric protein is localized in the nucleus. A normal AML1 protein of 27 kDa was also detected in t(8;21) Kasumi-1 cells. It remains to be established by which mechanism the mutant AML1 isoform may contribute to the leukemogenesis process of t(8;21)-positive acute myeloid leukemia.

A clinicopathologic study of 100 cases of Parkinson's disease.

The clinical details of 100 cases of histologically confirmed Parkinson's disease were examined and correlated with pathologic findings. Age at disease onset (mean, 62.4 years), disease duration (mean, 13.1 years), and age at death (mean, 75.5 years) were similar to those in previous smaller series. Asymmetric, tremulous onset was most common, although 23% of patients had no rest tremor. Motor fluctuations and dyskinesias occurred in 60% of levodopa-treated patients. All patients had clinical parkinsonism; however, 12 had atypical clinical features of Parkinson's disease, including severe early dementia, fluctuating confusional states, no response to levodopa, and early marked autonomic disturbance. Neuropathologic examination found coexistent Alzheimer-type change in 17 cases and striatal abnormality--mainly vascular--in 34 cases. Cortical Lewy bodies were present in all cases, but only four satisfied proposed criteria for diffuse Lewy body disease. Dementia occurred in 44% of cases; 29% had Alzheimer's disease, 10% had numerous cortical Lewy bodies, and 6% had a possible vascular cause; in 55% no definite pathologic cause was found. Nigral cell loss correlated with disease duration and severity. Although the general pattern of disease conformed to traditional descriptions, the findings broaden the present clinical and pathologic spectrum of Parkinson's disease.

Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease.

OBJECTIVE: The clinical recognition of multiple system atrophy (MSA) in patients presenting with parkinsonian signs is difficult. We attempted to verify the predictive value of some pointers that are used in clinical practice. DESIGN: Sixteen consecutive patients with pathologically confirmed MSA who presented with a parkinsonian syndrome over an 8-year period were studied retrospectively, and their clinical features were analyzed in detail. SETTING: Parkinson's Disease Society, Brain Tissue Bank, Institute of Neurology, London, England. PATIENTS: Sixteen patients with pathologically proven MSA who presented with parkinsonian syndrome in the first 3 years since disease onset. METHODS: Clinical features that were analyzed included the rapidity of disease progression, the relative symmetry of symptom onset, the presence or absence of tremor at initial presentation, the therapeutic response to levodopa and the associated presence of autonomic dysfunction. Fourteen of the 16 patients also had a computed tomographic scan of the brain performed. The frequency of selected items in MSA was compared with that found in 20 pathologically confirmed cases of Parkinson's disease and 16 pathologically confirmed cases of progressive supranuclear palsy (Steele-Richardson-Olszewski disease). RESULTS: It was found that a probability scale based on five selected items discriminated MSA with a pure parkinsonian presentation from Parkinson's disease, but not from progressive supranuclear palsy. Patients affected by the latter disorder, however, commonly presented with additional clinical features (supranuclear vertical down-gaze palsy, axial dystonia, and cognitive impairment), which helped to differentiate it from MSA.