Spatial variations in aromatic hydrocarbon emission in a dust-rich galaxy.

Dust grains absorb half of the radiation emitted by stars throughout the history of the universe, re-emitting this energy at infrared wavelengths1-3. Polycyclic aromatic hydrocarbons (PAHs) are large organic molecules that trace millimetre-size dust grains and regulate the cooling of interstellar gas within galaxies4,5. Observations of PAH features in very distant galaxies have been difficult owing to the limited sensitivity and wavelength coverage of previous infrared telescopes6,7. Here we present James Webb Space Telescope observations that detect the 3.3 µm PAH feature in a galaxy observed less than 1.5 billion years after the Big Bang. The high equivalent width of the PAH feature indicates that star formation, rather than black hole accretion, dominates infrared emission throughout the galaxy. The light from PAH molecules, hot dust and large dust grains and stars are spatially distinct from one another, leading to order-of-magnitude variations in PAH equivalent width and ratio of PAH to total infrared luminosity across the galaxy. The spatial variations we observe suggest either a physical offset between PAHs and large dust grains or wide variations in the local ultraviolet radiation field. Our observations demonstrate that differences in emission from PAH molecules and large dust grains are a complex result of localized processes within early galaxies.

Biomechanical and ergonomic risks associated with cervical musculoskeletal dysfunction amongst surgeons: A systematic review.

INTRODUCTION: Surgeons are at high risk of developing musculoskeletal symptoms due to a range of factors including, maladaptive positioning and surgical ergonomics. Cervical muscle strain and biomechanical load is most prevalent due to repetitive motions and prolonged static neck positioning. This issue is apparent through reports of prevalence between 10 and 74.4% among surgeons. The aim of this systematic review is to provide an objective assessment of the clinical evidence available and a descriptive analysis of the effects of kinematics and surgical ergonomics on the prevalence of surgeons' cervical musculoskeletal pain. METHODS: This is PRISMA-compliant systematic review of clinical studies assessing the prevalence of cervical musculoskeletal dysfunction in surgeons by searching PUBMED and Ovid EMBASE databases from inception to 19th October 2023. Study quality was graded according to the National Institutes of Health study quality assessment tools. RESULTS: A total of 9 studies were included in the final qualitative analysis. The use of loupes, open surgery and excessive neck flexion (>30°) were associated with cervical dysfunction. Comparison of study outcomes was challenging due to heterogeneity within study methods and the paucity of methodological quality. CONCLUSION: The current literature assessing ergonomic and biomechanical factors predisposing surgeons to cervical musculoskeletal dysfunction is insufficient to provide reliable guidance for clinicians. Although the literature identifies factors contributing to work-related cervical dysfunction, few attempt to evaluate interventions for improved surgical ergonomics. An objective assessment of interventions that prompt postural correction with the aim to improve neck pain in surgeon cohorts is warranted.

Bone and soft tissue tumors: clinicoradiologic-pathologic molecular-genetic correlation of novel fusion spindled, targetable-ovoid, giant-cell-rich, and round cell sarcomas.

BACKGROUND: New entities in the classification of bone and soft tissue tumors have been identified by use of advanced molecular-genetic techniques, including next-generation sequencing. Clinicoradiologic and pathologic correlation supports diagnostic classification. METHODS: Tumors from four morphologically grouped areas are selected to enhance diagnosis and awareness among the multidisciplinary team. These include select round cell tumors, spindle cell tumors, targetable tyrosine kinase/RAS::MAPK pathway-ovoid (epithelioid to spindled) tumors, and giant-cell-rich tumors of bone and soft tissue. RESULTS: Round cell tumors of bone and soft tissue include prototypical Ewing sarcoma, newer sarcomas with BCOR genetic alteration and CIC-rearranged, as well as updates on FUS/EWSR1::NFATc2, an EWSR1 non-ETS tumor that is solid with additional amplified hybridization signal pattern of EWSR1. This FUS/EWSR1::NFATc2 fusion has now been observed in seemingly benign to low-grade intraosseous vascular-rich and simple (unicameral) bone cyst tumors. Select spindle cell tumors of bone and soft tissue include rhabdomyosarcoma with FUS/EWSR1::TFCP2, an intraosseous high-grade spindle cell tumor without matrix. Targetable tyrosine-kinase or RAS::MAPK pathway-tumors of bone and soft tissue include NTRK, ALK, BRAF, RAF1, RET, FGFR1, ABL1, EGFR, PDGFB, and MET with variable ovoid myopericytic to spindled pleomorphic features and reproducible clinicopathologic and radiologic clues to their diagnosis. Giant-cell-rich tumors of bone, joint, and soft tissue are now respectively characterized by H3F3A mutation, CSF1 rearrangement (targetable), and HMGA2::NCOR2 fusion. CONCLUSION: This article is an update for radiologists, oncologists, surgeons, and pathologists to recognize these novel ovoid, spindled, giant-cell-rich, and round cell tumors, for optimal diagnostic classification and multidisciplinary team patient care.

Implementing Implementation Research: Teaching Implementation Research to HIV Researchers.

PURPOSE OF REVIEW: Given the growth in HIV-related implementation research, there is a need to expand the workforce and rigor through implementation science (IS) training and mentorship. Our objective is to review IS training opportunities for HIV-focused researchers and describe the approach and lessons learned from a recent HIV-related implementation research training initiative. RECENT FINDINGS: IS training opportunities range from degree programs to short- and longer-term professional development institutes and community-focused institutional trainings. Until recently, there have not been extensive dedicated opportunities for implementation research training for HIV-focused investigators. To meet this gap, an inter-Center for AIDS Research IS Fellowship for early-stage investigators was launched in 2019, building on lessons learned from dissemination and implementation training programs. Key components of the HIV-focused IS fellowship include didactic training, mentorship, grant-writing, and development of HIV-IS collaborative networks. Fellows to-date were two-thirds junior faculty and one-third post-doctoral fellows, the majority (69%) with prior public health training. Perceived value of the program was high, with a median rating of 9 [IQR 8-9] on a 10-point scale. Overall, 22/27 (81%) Fellows from the first cohort submitted IS-related grants within 12 months of Fellowship completion, and by 1 year 13 grants had been funded among 10 investigators, 37% overall among Fellows. Mentors identified framing of IS questions as the top-ranked training priority for HIV-investigators. Increasing knowledge of the utility of IS may support more grants focused on optimal implementation of HIV treatment and prevention strategies. Experiences from mentors and trainees engaged in an IS-focused fellowship for HIV investigators demonstrate the demand and value of a dedicated training program and reinforce the importance of mentorship.

Translating evidence-based parenting programs for primary care: Stakeholder recommendations for sustainable implementation.

AIMS: To translate evidence-based programs (EBP) for a new setting, attention must be given to the characteristics of the intervention and the local setting, as well as evidence that is compelling to decision-makers. This paper describes the history of a partnership and stakeholder recommendations to inform the adaptation of an EBP for primary care. METHODS: We established a community advisory board (CAB) consisting of stakeholders with expertize in primary care delivery. A thematic analysis was conducted with fieldnotes and transcriptions from CAB meetings and regular meetings with participating clinics. RESULTS: We found that (a) parenting programs with a focus on behavioral and physical health are appropriate for this setting, (b) variability in the structure of primary care means implementation must be tailorable, and (c) financial and organizational outcomes are compelling for decision-makers. CONCLUSION: Factors related to the content and structure of evidence-based programs are uniquely related to distinct implementation outcomes of interest to key stakeholders.

Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.

Statins are widely prescribed to lower plasma low-density lipoprotein (LDL) cholesterol levels. They also modestly reduce plasma triglyceride (TG), an independent cardiovascular disease risk factor, in most people. The mechanism and inter-individual variability of TG statin response is poorly understood. We measured statin-induced gene expression changes in lymphoblastoid cell lines derived from 150 participants of a simvastatin clinical trial and identified 23 genes (false discovery rate, FDR=15%) with expression changes correlated with plasma TG response. The correlation of insulin-induced gene 1 (INSIG1) expression changes with TG response (rho=0.32, q=0.11) was driven by men (interaction P=0.0055). rs73161338 was associated with INSIG1 expression changes (P=5.4 × 10-5) and TG response in two statin clinical trials (P=0.0048), predominantly in men. A combined model including INSIG1 expression level and splicing changes accounted for 29.5% of plasma TG statin response variance in men (P=5.6 × 10-6). Our results suggest that INSIG1 variation may contribute to statin-induced changes in plasma TG in a sex-specific manner.

Dual-grating dielectric accelerators driven by a pulse-front-tilted laser.

This paper investigates numerically dual-grating dielectric laser-driven accelerators driven by a pulse-front-tilted (PFT) laser, which extends the interaction length and boosts the electrons' energy gain. The optical system necessary to generate PFT laser beams with an ultrashort pulse duration of 100 fs is also studied in detail. Through two-dimensional particle-in-cell simulations, we show that such a PFT laser effectively increases the energy gain by (91±25) % compared to that of a normally incident laser with a waist radius of 50 µm for a 100-period dual-grating structure.

Shunting of the over 80s in normal pressure hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus is predominantly a disease of the elderly. By its nature, many of those who present to clinic are in advanced old age with multiple comorbidities. Majority of patients treated are younger than 80 years old. We present the clinical outcomes and complication rates of patients over the age of 80 years at the time of operation, during the past 11 years at a single institution. METHODS: Retrospective analysis of clinical records of all patients over the age of 80 years, who presented to our institution between 2006 and 2016. Results were analysed for co-morbidities, immediate and delayed complications, change in mobility/cognitive function post shunting of hydrocephalus. RESULTS: 39 patients (24 male, 15 female) met criteria. Mean [SD] age at the time of shunt insertion was 84 years (+/- 3.22) (range 80-94). No patients developed immediate CSF infection or sub-dural collection, or extended length of stay due to surgical or anaesthetic complications. There were no peri-operative or anaesthetic complications. 4 patients required a delayed surgical revision to encourage greater CSF drainage. 3 patients went on to develop delayed subdural haematoma, 1 of which was associated with trauma, 2 through overdrainage. 1 patient experienced poor post-operative wound healing and subsequently underwent removal of shunt. Of the 34 patient followed up, 27 patients (79.4%) improved in their mobility. (64.7%) patients/families reported symptomatic improvement in their cognition and memory. 6 (17.7%) patients did not experience an improvement in either mobility or cognitive function. CONCLUSIONS: Our data supports the assertion that, with proper patient selection, shunting of the over 80s with iNPH is a safe and effective procedure.

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. METHOD: Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. RESULTS: When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. CONCLUSIONS: In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

Constant pH simulations of pH responsive polymers.

Polyacidic polymers can change structure over a narrow range of pH in a competition between the hydrophobic effect, which favors a compact state, and electrostatic repulsion, which favors an extended state. Constant pH molecular dynamics computer simulations of poly(methacrylic acid) reveal that there are two types of structural changes, one local and one global, which make up the overall response. The local structural response depends on the tacticity of the polymer and leads to different cooperative effects for polymers with different stereochemistries, demonstrating both positive and negative cooperativities.

Comparison of Two US Sheep Scrapie Isolates Supports Identification as Separate Strains.

Scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics. However, in the United States, very little is known about the potential presence of scrapie strains. Scrapie strain and PRNP genotype could both affect susceptibility, potential for transmission, incubation period (IP), and control measures required for eliminating scrapie from a flock. The investigators evaluated 2 US scrapie isolates, No. 13-7 and x124, after intranasal inoculation to compare clinical signs, IPs, spongiform lesions, and patterns of PrPSc deposition in sheep with scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124, susceptibility and IP were associated with valine at codon 136 (V136) of the prion protein: VV136 sheep had short IPs (6.9 months), those in AV136 sheep were 11.9 months, and AA136 sheep did not develop scrapie. All No. 13-7 inoculated sheep developed scrapie, with IPs of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep, and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were influenced by inoculum isolate and host genotype. Differences in PrPSc profiles versus isolate were most striking when examining brains from sheep with the VV136 genotype. Inoculation into C57BL/6 mice resulted in markedly different attack rates (90.5% for x124 and 5.9% for No. 13-7). Taken together, these data demonstrate that No. 13-7 and x124 represent 2 distinct strains of scrapie with different IPs, genotype susceptibilities, and PrPSc deposition profiles.

When do we think it is Safe to Drive after Hand Surgery? - Current Practice and Legal Perspective.

Patients recovering from hand surgery frequently ask when it is safe to drive and it is unclear where the responsibility lies; the surgeon, the patient or the insurance company. An eight-question survey looking at various aspects of clinical practice was circulated to consultant and trainee plastic and orthopaedic surgeons in Ireland and the UK. Of the 89 surgeons who replied, (53%) felt the decision when to drive was the patient's compared with the insurance company (40%) and the surgeon (7%). 80% advised patients to contact their insurance company. 87% were unaware of current regulations or guidelines. National guidelines were vague and left the decision with the treating doctor. Similarly, major insurers advise patients to contact their doctor for advice. From a legal standpoint, the patient has a duty of care to other road users to be in full control of his vehicle prior to driving, regardless of any advice received.

Boundary-Layer Effects on Acoustic Transmission Through Narrow Slit Cavities.

We explore the slit-width dependence of the resonant transmission of sound in air through both a slit array formed of aluminum slats and a single open-ended slit cavity in an aluminum plate. Our experimental results accord well with Lord Rayleigh's theory concerning how thin viscous and thermal boundary layers at a slit's walls affect the acoustic wave across the whole slit cavity. By measuring accurately the frequencies of the Fabry-Perot-like cavity resonances, we find a significant 5% reduction in the effective speed of sound through the slits when an individual viscous boundary layer occupies only 5% of the total slit width. Importantly, this effect is true for any airborne slit cavity, with the reduction being achieved despite the slit width being on a far larger scale than an individual boundary layer's thickness. This work demonstrates that the recent prevalent loss-free treatment of narrow slit cavities within acoustic metamaterials is unrealistic.

Generalized Lotka stability.

The recently developed macroscopic approach to demography describes the age distribution of mothers and the net maternity function for a given human population entirely in terms of five parameters. Tracking of these parameters provides a number of new tools for analyzing populations and predicting their future states. Within the macroscopic approach, the new concept of generalized Lotka stability is presented in this paper, as an extension of a strong version of classic Lotka stability. The two leading parameters of the macroscopic approach, the Malthusian parameter r and the perturbation s, are computed from population data and plotted in two-dimensional parameter space. Generalized Lotka stability is then defined in terms of the movement of the (r,s)-vector over time. It may be observed in a number of human populations at specific periods of their history.

Association of maternal anti-HLA class II antibodies with protection from allergy in offspring.

BACKGROUND: Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years. METHODS: Anti-HLA class I and II antibodies were measured in maternal serum (n = 284) and levels correlated to numbers of pregnancies and birth order, and allergic outcomes in offspring at 8 years of age. RESULTS: Maternal anti-HLA class I and II antibodies were significantly higher when birth order, and the number of pregnancies were larger. Anti-HLA class II, but not class I antibodies were associated with significantly less atopy and seasonal rhinitis in the offspring at age 8 years. Mothers with nonatopic (but not atopic) offspring had a significant increase in anti-HLA class I and II antibodies with birth order. CONCLUSION: This study suggests that the 'birth order' effect in children may be due to parity-related changes in the maternal immune response to foetal antigens. We have observed for the first time an association between maternal anti-HLA class II antibodies and protection from allergy in the offspring. Further work is required to determine immunologically how HLA disparity between mother and father can protect against allergy.

Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides.

The apolipoprotein E (APOE) E4 allele is associated with Alzheimer's disease, cardiovascular disease, and decreased longevity. To probe the mechanism of these associations, cell lines were created which secrete each apoE isoform. ApoE conditioned media, purified apoE, and commercially obtained apoE protected B12 cells from hydrogen peroxide cytotoxicity with E2 > E3 > E4. Physiological levels of apoE protected cells from beta-amyloid peptides, while higher doses of apoE led to increased cytotoxicity. E2 > E3 > E4 possessed antioxidant activity, and apoE bound certain metal ions. The decreased antioxidant activity of E4 could contribute to its association with Alzheimer's disease, cardiovascular disease and decreased longevity.

Severe epigastric pain following a birthday party.

Epigastric pain is a very common symptom which can be caused by a wide range of clinical conditions. A 28 year old male presented to our clinic with new onset severe epigastric pain. As part of the routine work up for pain of this nature, we proceeded to upper gastrointestinal endoscopy. A toothpick was found lodged in the antral gastric wall with a resulting inflammatory mass abutting the free edge. It was removed successfully with full resolution of symptoms, however a review of the literature shows that ingested toothpicks can cause major morbidity.

Quantitative estimation of closed cell porosity in low density ceramic composites using X-ray microtomography.

X-ray Microtomography is a proven tool for phase fraction analysis of multi-phase systems, provided that each phase is adequately partitioned by some means of data processing. For porosity in materials containing low-density ceramic phases, differentiation between pores and the low-density phase(s) can be intractable due to low scattering in the low-density phase, particularly if small pores necessitate low binning. We present a novel, combined methodology for accurate porosity analysis-despite these shortcomings. A 3-stage process is proposed, consisting of (1) Signal/noise enhancement using non-local means denoising, (2) Phase segmentation using a convolutional neural network, and (3) Quantitative analysis of the resulting 3D pore metrics. This particular combination of denoising and segmentation is robust against the fragmentation of common segmentation algorithms, while avoiding the volitional aspects of model selection associated with histogram fitting. We discuss the procedure applied to ternary phase SiC-TiC-diamond composites produced by reactive spark plasma sintering with porosity spanning 2-9 vol%.

Comparison of Body Composition Methods for Estimating Body Fat Percentage in Lower Limb Prosthesis Users.

BACKGROUND: There is a dearth of literature evaluating the accuracy of Air Displacement Plethysmography (ADP) compared to Dual-energy X-ray Absorptiometry (DXA) for assessing body composition in individuals with lower limb amputations. Validity of ADP in persons with lower limb amputations must be established. OBJECTIVE: The objective of this study was to compare body composition in persons with lower limb amputations using the BOD POD® and DXA. METHODOLOGY: Body composition was performed on eleven lower limb prosthesis users (age 53.2±14.3 years, weight 81.9±22.3kg) using ADP and DXA with and without prosthesis. FINDINGS: Repeated measures ANOVA indicated no significant difference in body composition among and between trials, F(3,8)= 3.36, p= 0.075. There were no significant differences in Body Fat (BF) percentage with and without prostheses on the BOD POD (28.5±15.7% and 33.7±12.1%, respectively) nor the DXA (32.9±10.6% and 32.0±9.9%, respectively). Association between the BOD POD and DXA were greatest when prostheses were not worn compared to when they were worn. Bland-Altman plots indicate agreement between BOD POD® and DXA was greatest while wearing the prosthesis. CONCLUSION: This study is a first to compare total body fat percent between the BOD POD® and DXA in lower limb prosthesis users. BOD POD® report valid indices of BF%. Future work will utilize the BOD POD® in intervention studies for monitoring body composition changes across the continuum of rehabilitation.