Factors associated with chronic depressive symptoms across adolescence and young adulthood: a UK birth cohort study.

AIMS: Identifying children and/or adolescents who are at highest risk for developing chronic depression is of utmost importance, so that we can develop more effective and targeted interventions to attenuate the risk trajectory of depression. To address this, the objective of this study was to identify young people with persistent depressive symptoms across adolescence and young adulthood and examine the prospective associations between factors and persistent depressive symptoms in young people. METHODS: We used data from 6711 participants in the Avon Longitudinal Study of Parents and Children. Depressive symptoms were assessed at 12.5, 13.5, 16, 17.5, 21 and 22 years with the Short Mood and Feelings Questionnaire, and we further examined the influence of multiple biological, psychological and social factors in explaining chronic depressive symptoms. RESULTS: Using latent class growth analysis, we identified four trajectories of depressive symptoms: persistent high, persistent low, persistent moderate and increasing high. After applying several logistic regression models, we found that loneliness and feeling less connected at school were the most relevant factors for chronic course of depressive symptoms. CONCLUSIONS: Our findings contribute with the identification of those children who are at highest risk for developing chronic depressive symptoms.

Adhesion-Lubrication Paradox of Articular Cartilage.

The friction of solids is primarily understood through the adhesive interactions between the surfaces. As a result, slick materials tend to be nonstick (e.g., Teflon), and sticky materials tend to produce high friction (e.g., tires and tape). Paradoxically, cartilage, the slippery bearing material of human joints, is also among the stickiest of known materials. This study aims to elucidate this apparent paradox. Cartilage is a biphasic material, and the most cited explanation is that both friction and adhesion increase as load transfers from the pressurized interstitial fluid to the solid matrix over time. In other words, cartilage is slippery and sticky under different times and conditions. This study challenges this explanation, demonstrating the strong adhesion of cartilage under high and low interstitial hydration conditions. Additionally, we find that cartilage clings to itself (a porous material) and Teflon (a nonstick material), as well as other surfaces. We conclude that the unusually strong interfacial tension produced by cartilage reflects suction (like a clingfish) rather than adhesion (like a gecko). This finding is surprising given its unusually large roughness, which typically allows for easy interfacial flow and defeats suction. The results provide compelling evidence that cartilage, like a clingfish, conforms to opposing surfaces and effectively seals submerged contacts. Further, we argue that interfacial sealing is itself a critical function, enabling cartilage to retain hydration, load support, and lubrication across long periods of inactivity.

Defence Engagement (Health) between the UK and Ireland since the Good Friday Agreement in 1998.

This paper describes the range of Defence Engagement (Health) (DE(H)) activities between Northern Ireland and Ireland following the Good Friday Agreement in April 1998. Although the Agreement made provision for cross-border cooperation in health, the Omagh bombing of August 1998 energised the discussion to provide greater co-ordination of future responses to mass casualty events. The paper describes these DE(H) activities at the Strategic, Operational and Tactical levels to show the integration across these levels and between the agencies of both governments. The paper shows how a DE(H) programme can have a successful strategic effect by finding topics of mutual interest that can bring together two countries in order to provide an effective health and social care provision. This paper forms part of a special issue of BMJ Military Health dedicated to Defence Engagement (.

Erector spinae plane block did not improve postoperative pain-related outcomes and recovery after video-assisted thoracoscopic surgery : a randomised controlled double-blinded multi-center trial.

INTRODUCTION: There is a sizable niche for a minimally invasive analgesic technique that could facilitate ambulatory video-assisted thoracoscopic surgery (VATS). Our study aimed to determine the analgesic potential of a single-shot erector spinae plane (ESP) block for VATS. The primary objective was the total hydromorphone consumption with patient-controlled analgesia (PCA) 24 h after surgery. METHODS: We conducted a randomized, controlled, double-blind study with patients scheduled for VATS in two major university-affiliated hospital centres. We randomized 52 patients into two groups: a single-shot ESP block using bupivacaine or an ESP block with normal saline (control). We administered a preoperative and postoperative (24 h) quality of recovery (QoR-15) questionnaire and assessed postoperative pain using a verbal numerical rating scale (VNRS) score. We evaluated the total standardized intraoperative fentanyl administration, total postoperative hydromorphone consumption (PCA; primary endpoint), and the incidence of adverse effects. RESULTS: There was no difference in the primary objective, hydromorphone consumption at 24 h (7.6 (4.4) mg for the Bupivacaine group versus 8.1 (4.2) mg for the Control group). Secondary objectives and incidence of adverse events were not different between the two groups at any time during the first 24 h following surgery. CONCLUSION: Our multi-centre randomized, controlled, double-blinded study found no advantage of an ESP block over placebo for VATS for opioid consumption, pain, or QoR-15 scores. Further studies are ongoing to establish the benefits of using a denser block (single-shot paravertebral with a continuous ESP block), which may provide a better quality of analgesia.

Observations and properties of the first laboratory fusion experiment to exceed a target gain of unity.

An indirect-drive inertial fusion experiment on the National Ignition Facility was driven using 2.05 MJ of laser light at a wavelength of 351 nm and produced 3.1±0.16 MJ of total fusion yield, producing a target gain G=1.5±0.1 exceeding unity for the first time in a laboratory experiment [Phys. Rev. E 109, 025204 (2024)10.1103/PhysRevE.109.025204]. Herein we describe the experimental evidence for the increased drive on the capsule using additional laser energy and control over known degradation mechanisms, which are critical to achieving high performance. Improved fuel compression relative to previous megajoule-yield experiments is observed. Novel signatures of the ignition and burn propagation to high yield can now be studied in the laboratory for the first time.

Arterial blood gas measurements are different for brachycephalic and nonbrachycephalic dogs acclimatized to an altitude of 1,535 meters.

OBJECTIVE: To define reference intervals (RIs) for arterial blood gas (aBG) measurements in healthy, nonsedated, dolichocephalic, and mesocephalic (nonbrachycephalic) dogs at approximately 1,535 m above sea level and compare these findings with healthy, nonsedated, brachycephalic dogs living at the same altitude. ANIMALS: 120 adult nonbrachycephalic dogs and 20 adult brachycephalic dogs. METHODS: Cases were prospectively enrolled from October 2021 to June 2022. Dogs were enrolled from the community or after presentation for wellness examinations or minor injuries including lacerations, nail injuries, and lameness. Physical examinations and systolic blood pressure (sBP) measurements were obtained before blood sample collection. Arterial blood was collected from the dorsal pedal artery or femoral artery. After data collection, brachycephalic dogs underwent pre- and postexercise tolerance assessments. RESULTS: The mean and RI values for arterial pH (7.442; 7.375 to 7.515), partial pressure of oxygen in arterial blood (Pao2; 78.3; 59.2 to 92.7 mm Hg), partial pressure of carbon dioxide in arterial blood (Paco2; 28.0; 21.5 to 34.4 mm Hg), saturation of arterial oxygen (Sao2; 98.4; 84.3% to 101.4%), HCO3 (18.9; 14.9 to 22.4 mmol/L), concentration of total hemoglobin (ctHb; 17.5; 13.4 to 21.1 g/dL), and sBP (133; 94 to 180 mm Hg) were established for healthy nonbrachycephalic dogs at 1,535-m altitude. All aBG measurements were statistically and clinically different from those previously reported for dogs at sea level. Brachycephalic dogs had significantly lower Pao2 and Sao2 (P = .0150 and P = .0237, respectively) and significantly higher ctHb (P = .0396) compared to nonbrachycephalic dogs acclimatized to the same altitude; the nonbrachycephalic RIs were not transferable to the brachycephalic dogs for Pao2. CLINICAL RELEVANCE: This study represents the first collation of aBG measurements for healthy nonbrachycephalic dogs acclimatized to an altitude of 1,535 m. Additionally, this study identified differences in arterial oxygenation measurements between brachycephalic and nonbrachycephalic dogs. RIs in brachycephalic dogs need to be established.

Hohlraum Reheating from Burning NIF Implosions.

As fusion experiments at the National Ignition Facility (NIF) approach and exceed breakeven, energy from the burning capsule is predicted to couple to the gold walls and reheat the hohlraum. On December 5, 2022, experiment N221204 exceeded target breakeven, historically achieving 3.15 MJ of fusion energy from 2.05 MJ of laser drive; for the first time, energy from the igniting capsule reheated the hohlraum beyond the peak laser-driven radiation temperature of 313 eV to a peak of 350 eV, in less than half a nanosecond. This reheating effect has now been unambiguously observed by the two independent Dante calorimeter systems across multiple experiments, and is shown to result from reheating of the remnant tungsten-doped ablator by the exploding core, which is heated by alpha deposition.

Differential effects of teriparatide, denosumab and zoledronate on hip structural and mechanical parameters in osteoporosis; a real-life study.

PURPOSE: The aim of this study was to evaluate changes in hip geometry parameters following treatment with teriparatide (TPD), denosumab (Dmab) and zoledronate (ZOL) in real-life setting. METHODS: We studied 249 patients with osteoporosis (OP) with mean [SD] age of 71.5 [11.1] years divided into 3 treatment groups; Group A received TPD; n = 55, Group B (Dmab); n = 116 and Group C (ZOL); n = 78 attending a routine metabolic bone clinic. Bone mineral density (BMD) was measured by DXA at the lumbar spine (LS), total hip (TH) and femoral neck (FN) prior to treatment and after 2 years (Group A), after a mean treatment duration of 3.3 [1.3] years (Group B) and after 1, 2 and 3 doses of ZOL (Group C) to assess treatment response. Hip structural analysis (HSA) was carried out retrospectively from DXA-acquired femur images at the narrow neck (NN), the intertrochanter (IT) and femoral shaft (FS). RESULTS: Changes in parameters of hip geometry and mechanical strength were seen in the following treatment. Percentage change in cross-sectional area (CSA): 3.56[1.6] % p = 0.01 and cross-sectional moment of inertia (CSMI): 4.1[1.8] % p = 0.029 increased at the NN only in Group A. Improvement in HSA parameters at the IT were seen in group B: CSA: 3.3[0.67]% p < 0.001, cortical thickness (Co Th): 2.8[0.78]% p = 0.001, CSMI: 5.9[1.3]% p < 0.001, section modulus (Z):6.2[1.1]% p < 0.001 and buckling ratio (BR): - 3.0[0.86]% p = 0.001 with small changes at the FS: CSA: 1.2[0.4]% p = 0.005, Z:1.6 [0.76]%, p = 0.04. Changes at the IT were also seen in Group C (after 2 doses): CSA: 2.5[0.77]% p = 0.017, Co Th: 2.4[0.84]% p = 0.012, CSMI: 3.9[1.3]% p = 0.017, Z:5.2[1.16]% p < 0.001 and BR: - 3.1[0.88]% p = 0.001 and at the NN (following 3 doses): outer diameter (OD): 4.0[1.4]% p = 0.0005, endocortical diameter(ED): 4.3[1.67% p = 0.009, CSA:5.2[1.8]% p = 0.003, CSMI: 9.3[3.8]% p = 0.019. CONCLUSIONS: Analysis of the effect of OP therapies on hip geometry is useful in understanding the mechanisms of their anti-fracture effect and may provide additional information on their efficacy.

Venture Capital in US Medicine: A Briefing for Radiologists.

In recent years, there has a been a rapid and significant drop in the number of private practices in US radiology. Many factors have driven this change. One of the most important has been the corporatization of practices. In many cases, this involves third-party financing, one type of which is venture capital. This article will provide an introduction to the venture capital investment model for medical professionals.

A review of Bland-Altman difference plot analysis in the veterinary clinical pathology laboratory.

Current guidelines recommend using Bland-Altman plots (BA-plots), also called Difference plots, as part of method comparison evaluation in the veterinary clinical pathology laboratory. Analysis of differences can meaningfully augment linear regression techniques and allows fuller summarization of the performance of two methods relative to each other. This work summarizes the current literature on BA-plot composition and evaluation. Model data is used to demonstrate data evaluation approaches based on the observed differences, the combined inherent imprecision of the methods, and clinically relevant performance goals. Common limitations of the approaches, including points of frequent misinterpretation, are presented. BA-plot analysis can be part of an intentionally crafted method comparison study that provides analytically and clinically relevant data.

Diagnosing the origin and impact of low-mode asymmetries in ignition experiments at the National Ignition Facility.

Inertial confinement fusion ignition requires high inflight shell velocity, good energy coupling between the hotspot and shell, and high areal density at peak compression. Three-dimensional asymmetries caused by imperfections in the drive symmetry or target can grow and damage the coupling and confinement. Recent high-yield experiments have shown that low-mode asymmetries are a key degradation mechanism and contribute to variability. We show the experimental signatures and impacts of asymmetry change with increasing implosion yield given the same initial cause. This letter has implications for improving robustness to a key degradation in ignition experiments.

Mn-porphyrins in a four-helix bundle participate in photo-induced electron transfer with a bacterial reaction center.

Hybrid complexes incorporating synthetic Mn-porphyrins into an artificial four-helix bundle domain of bacterial reaction centers created a system to investigate new electron transfer pathways. The reactions were initiated by illumination of the bacterial reaction centers, whose primary photochemistry involves electron transfer from the bacteriochlorophyll dimer through a series of electron acceptors to the quinone electron acceptors. Porphyrins with diphenyl, dimesityl, or fluorinated substituents were synthesized containing either Mn or Zn. Electrochemical measurements revealed potentials for Mn(III)/Mn(II) transitions that are ~ 0.4 V higher for the fluorinated Mn-porphyrins than the diphenyl and dimesityl Mn-porphyrins. The synthetic porphyrins were introduced into the proteins by binding to a four-helix bundle domain that was genetically fused to the reaction center. Light excitation of the bacteriochlorophyll dimer of the reaction center resulted in new derivative signals, in the 400 to 450 nm region of light-minus-dark spectra, that are consistent with oxidation of the fluorinated Mn(II) porphyrins and reduction of the diphenyl and dimesityl Mn(III) porphyrins. These features recovered in the dark and were not observed in the Zn(II) porphyrins. The amplitudes of the signals were dependent upon the oxidation/reduction midpoint potentials of the bacteriochlorophyll dimer. These results are interpreted as photo-induced charge-separation processes resulting in redox changes of the Mn-porphyrins, demonstrating the utility of the hybrid artificial reaction center system to establish design guidelines for novel electron transfer reactions.

Neutron time of flight (nToF) detectors for inertial fusion experiments.

Neutrons generated in Inertial Confinement Fusion (ICF) experiments provide valuable information to interpret the conditions reached in the plasma. The neutron time-of-flight (nToF) technique is well suited for measuring the neutron energy spectrum due to the short time (100 ps) over which neutrons are typically emitted in ICF experiments. By locating detectors 10s of meters from the source, the neutron energy spectrum can be measured to high precision. We present a contextual review of the current state of the art in nToF detectors at ICF facilities in the United States, outlining the physics that can be measured, the detector technologies currently deployed and analysis techniques used.

Dynamics and Power Balance of Near Unity Target Gain Inertial Confinement Fusion Implosions.

The change in the power balance, temporal dynamics, emission weighted size, temperature, mass, and areal density of inertially confined fusion plasmas have been quantified for experiments that reach target gains up to 0.72. It is observed that as the target gain rises, increased rates of self-heating initially overcome expansion power losses. This leads to reacting plasmas that reach peak fusion production at later times with increased size, temperature, mass and with lower emission weighted areal densities. Analytic models are consistent with the observations and inferences for how these quantities evolve as the rate of fusion self-heating, fusion yield, and target gain increase. At peak fusion production, it is found that as temperatures and target gains rise, the expansion power loss increases to a near constant ratio of the fusion self-heating power. This is consistent with models that indicate that the expansion losses dominate the dynamics in this regime.

MUM1/IRF4 immunolabeling of neoplastic Langerhans histiocytes in a putative case of canine Langerhans cell histiocytosis.

Langerhans cell histiocytosis is a systemic histiocytic proliferative disease with cutaneous manifestations which is well described in human medical literature and has relatively recently been reclassified as a neoplastic disorder. The diagnosis of canine Langerhans cell histiocytosis has been proposed in the veterinary literature to refer to a histiocytic proliferative disease in the dog with clinical and histopathologic features that mirror the human disease. However, reports that invoke this diagnosis are rare and often lack complete diagnostic characterization. This case report presents an extensive diagnostic investigation of a putative case of Langerhans cell histiocytosis in a 3-year-old male castrated Golden Retriever dog, including gross, cytologic, histopathologic, and immunohistochemical findings. Furthermore, we document that canine LCH may have positive immunolabeling for the transcription factor multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4), which is classically used for the diagnosis of canine plasma cell neoplasms.

Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project.

BACKGROUND: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic 'second-hit' variants. METHODS: To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity. RESULTS: Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion in CFTR and a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2-6 of ENPP1. Although ambiguous by short-read WGS, the ENPP1 variant structure was resolved using optical genome mapping and RNA analysis. CONCLUSION: Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.

Fiber reinforced hydrated networks recapitulate the poroelastic mechanics of articular cartilage.

The role of poroelasticity on the functional performance of articular cartilage has been established in the scientific literature since the 1960s. Despite the extensive knowledge on this topic there remain few attempts to design for poroelasticity and to our knowledge no demonstration of an engineered poroelastic material that approaches the physiological performance. In this paper, we report on the development of an engineered material that begins to approach physiological poroelasticity. We quantify poroelasticity using the fluid load fraction, apply mixture theory to model the material system, and determine cytocompatibility using primary human mesenchymal stem cells. The design approach is based on a fiber reinforced hydrated network and uses routine fabrication methods (electrohydrodynamic deposition) and materials (poly[ɛ-caprolactone] and gelatin) to develop the engineered poroelastic material. This composite material achieved a mean peak fluid load fraction of 68%, displayed consistency with mixture theory, and demonstrated cytocompatibility. This work creates a foundation for designing poroelastic cartilage implants and developing scaffold systems to study chondrocyte mechanobiology and tissue engineering. STATEMENT OF SIGNIFICANCE: Poroelasticity drives the functional mechanics of articular cartilage (load bearing and lubrication). In this work we develop the design rationale and approach to produce a poroelastic material, known as a fiber reinforced hydrated network (FiHy™), that begins to approach the native performance of articular cartilage. This is the first engineered material system capable of exceeding isotropic linear poroelastic theory. The framework developed here enables fundamental studies of poroelasticity and the development of translational materials for cartilage repair.

Mass spectrometric-based assessment of the serum kappa to lambda immunoglobulin light chain ratio (κ:λ) in dogs with immunoglobulin secretory diseases.

The ratio of κ light chains to λ light chains (κ:λ) in serum is used as a biomarker of immunoglobulin secreting neoplasia in humans but has not been evaluated in dogs. A mass-spectrometry based method for determining the canine serum κ:λ was developed and used to evaluate samples from control dogs, dogs with an infectious aetiology, dogs with secretory plasma cell tumours (sPCT) and dogs with non-secretory B cell neoplasia. A human-targeted immunoturbidometric κ:λ assay and immunofixation using antisera targeting human κ light chain or λ light chain was also performed on all samples. Using whole serum samples, the MS-based κ:λ method identified 5 sPCT as κ-predominant (mean κ:λ = 3.307) and 5 sPCT as λ-predominant (mean κ:λ = 0.023) and documented differences between these groups and all other groups (p < 0.05 for all). The infectious aetiology group had a lower mean κ:λ ratio (mean κ:λ = 0.069) than control samples (mean κ:λ = 0.103, p = 0.035). Similar results were obtained when samples were enriched for proteins between 10 and 50 kDa using size exclusion chromatography, except for the statistical difference between the control and infectious aetiology group. All λ-predominant cases had only anti-human λ light chain labelling by immunofixation. Three κ-predominant cases had only anti-human κ-light chain labelling and the remaining two cases did not label with either antisera by immunofixation. The immunoturbidometric method had high analytical CV% (λ light chain CV = 13%, κ light chain CV = 50%), was unable to measure light chains in 20.5% of samples and did not distinguish groups. The data suggests that the human-targeted immunoturbidometric method would not be diagnostically useful and that the MS-derived serum κ:λ may be a useful biomarker of canine immunoglobulin secretory neoplasia which may have the ability to distinguish neoplasia from infectious causes of immunoglobulin secretion.

Multiple myeloma presenting as blepharitis in a horse.

Myeloma-related disorders, including multiple myeloma, extramedullary plasmacytoma, and solid osseous plasmacytoma, are rare in horses. Clinical complaints for myeloma-related disorders are nonspecific, and when present, M-protein location is more variable on protein electrophoresis in horses relative to dogs and cats. Here, we describe a case of a 15-year-old Thoroughbred mare who presented with recurrent blepharitis. Marked hyperglobulinemia was an incidental finding on routine hematologic and biochemical testing. Bone marrow aspiration consisted of >30% plasma cells, and serum protein electrophoresis demonstrated a monoclonal gammopathy in the alpha 2 fraction leading to a diagnosis of multiple myeloma. Immunofixation and radial immunodiffusion confirmed the presence of an IgG M-protein. Based on a restricted peak in the alpha 2 location, the specific M-protein is suspected to be IgG(T), an IgG isotype unique to horses. M-protein migration in horses is variable relative to dogs and cats, yet immunofixation can still be used to identify equine IgG M-protein isotypes. The unique clinical presentation in this case also serves as a reminder to consider neoplasia in horses with unusual or nonspecific clinical signs.