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Phenomenon: Marginalized individuals in medicine face many structural inequities which can have enduring consequences on their progress. Therefore, inequity must be addressed by dismantling underlying unjust policies, environments, and curricula. However, once these injustices have been taken apart, how do we build more just systems from the rubble? Many current strategies to address this question have foundational values of urgency, solutionism, and top-down leadership., Approach: This paper explores a counternarrative: Design Justice. As a set of guiding principles, Design Justice centers the experiences and perspectives of marginalized individuals and communities. These principles include mutual accountability and transparency, co-ownership, and community-led outcomes, and honoring local, traditional, Indigenous knowledge., Findings: Rooted in critical scholarship and critical design, Design Justice recognizes the interconnectedness of various forms of marginalization and works to critically examine power dynamics that exist in every design process. These co-created principles act as practical guardrails, directing progress toward justice., Insights: This paper begins with an overview of Design Justice's history in critical scholarship and critical design, providing foundational background knowledge for medical educators, scholars, and leaders in key concepts of justice and design. We explore how the Design Justice principles were developed and have been applied across sectors, highlighting its applications, including education applications. Finally, we raise critical questions about medical education prompted by Design Justice.

Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs). NETs counteract microbes but are also linked to inflammation in atherosclerosis, arthritis, or psoriasis by unknown mechanisms. Here, we report that NET-associated RNA (naRNA) stimulates further NET formation in naive PMNs via a unique TLR8-NLRP3 inflammasome-dependent pathway. Keratinocytes respond to naRNA with expression of psoriasis-related genes (e.g., IL17, IL36) via atypical NOD2-RIPK signaling. In vivo, naRNA drives temporary skin inflammation, which is drastically ameliorated by genetic ablation of RNA sensing. Unexpectedly, the naRNA-LL37 'composite damage-associated molecular pattern (DAMP)' is pre-stored in resting neutrophil granules, defining sterile NETs as inflammatory webs that amplify neutrophil activation. However, the activity of the naRNA-LL37 DAMP is transient and hence supposedly self-limiting under physiological conditions. Collectively, upon dysregulated NET release like in psoriasis, naRNA sensing may represent both a potential cause of disease and a new intervention target., (© 2024. The Author(s).)

Three-dimensional (3D) human skin equivalents have emerged as valuable tools in skin research, replacing animal experimentation and precluding the need for patient biopsies. In this study, we advanced 3D skin equivalents to model the inflammatory skin diseases atopic dermatitis and psoriasis by cytokine stimulation, and were successful in integrating TH1 T cells into skin models to develop an immunocompetent 3D psoriasis model. We performed in-depth histological and functional characterization of 3D skin equivalents and validated them in terms of tissue architecture, pathological changes, expression of antimicrobial peptides and Staphylococcus aureus colonization using 3D reconstruction by multiphoton microscopy and phenotyping by highly multiplexed 'co-detection by indexing' (CODEX) microscopy. We show that our skin equivalents have a structural architecture with a well-developed dermis and epidermis, thus resembling human skin. In addition, the skin models of atopic dermatitis and psoriasis show several phenotypic features of inflammatory skin disease, including disturbed epidermal differentiation and alterations in the expression of epidermal barrier genes and antimicrobial peptides, and can be reliably used to test novel treatment strategies. Therefore, these 3D equivalents will be a valuable tool in experimental dermatological research., Competing Interests: Competing interests C.M.S. is a scientific advisor to AstraZeneca PLC, and is on the scientific advisory board of, has stock options in, and has received research funding from Enable Medicine, Inc., all outside the current work. All other authors declare no competing financial and commercial interests., (© 2024. Published by The Company of Biologists Ltd.)

Staphylococcus aureus is the most common cause of bacterial skin infections in humans, including patients with atopic dermatitis (AD). Polymorphonuclear neutrophils (PMNs) are the first cells to infiltrate an infection site, where they usually provide an effective first line of defense, including neutrophil extracellular trap (NET) formation. Here, we show that infiltrating PMNs in inflamed human and mouse skin enhance S. aureus skin colonization and persistence. Mechanistically, we demonstrate that a crosstalk between keratinocytes and PMNs results in enhanced NET formation upon S. aureus infection, which in turn induces oxidative stress and expression of danger-associated molecular patterns such as high-mobility-group-protein B1 (HMGB1) in keratinocytes. In turn, HMGB1 enhances S. aureus skin colonization and persistence by promoting skin barrier dysfunctions by the downregulation of epidermal barrier genes. Using patient material, we show that patients with AD exhibit enhanced presence of PMNs, NETs, and HMGB1 in the skin, demonstrating the clinical relevance of our finding., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Keratinocytes form a multilayer barrier that protects the skin from invaders or injuries. The barrier function of keratinocytes is in part mediated by the production of inflammatory modulators that promote immune responses and wound healing. Skin commensals and pathogens such as Staphylococcus aureus secrete high amounts of phenol-soluble modulin (PSM) peptides, agonists of formyl-peptide receptor 2 (FPR2). FPR2 is crucial for the recruitment of neutrophils to the sites of infection, and it can influence inflammation. FPR1 and FPR2 are also expressed by keratinocytes but the consequences of FPR activation in skin cells have remained unknown., Methods: Since an inflammatory environment influences S. aureus colonization, e. g. in patients with atopic dermatitis (AD), we hypothesized that interference with FPRs may alter keratinocyte-induced inflammation, proliferation, and bacterial colonization of the skin. To assess this hypothesis, we investigated the effects of FPR activation and inhibition in keratinocytes with respect to chemokine and cytokine release as well as proliferation and skin wound gap closure., Results: We observed that FPR activation induces the release of IL-8, IL-1α and promotes keratinocyte proliferation in a FPR-dependent manner. To elucidate the consequence of FPR modulation on skin colonization, we used an AD-simulating S. aureus skin colonization mouse model using wild-type (WT) or Fpr2 -/- mice and demonstrate that inflammation enhances the eradication of S. aureus from the skin in a FPR2-dependent way. Consistently, inhibition of FPR2 in the mouse model or in human keratinocytes as well as human skin explants promoted S. aureus colonization., Discussion: Our data indicate that FPR2 ligands promote inflammation and keratinocyte proliferation in a FPR2-dependent manner, which is necessary for eliminating S. aureus during skin colonization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lebtig, Scheurer, Muenkel, Becker, Bastounis, Peschel and Kretschmer.)

Stress-related somatic and psychiatric disorders are often associated with a decline in regulatory T cell (Treg) counts and chronic low-grade inflammation. Recent preclinical evidence suggests that the latter is at least partly mediated by stress-induced upregulation of toll-like receptor (TLR)2 in newly generated neutrophils and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as glucocorticoid (GC) resistance in predominantly PMN-MDSCs following stress-induced upregulation of TLR4 expression. Here we show in mice exposed to the chronic subordinate colony housing (CSC) paradigm that repeated intragastric (i.g.) administrations of a heat-killed preparation of Mycobacterium vaccae NCTC 11659, a saprophytic microorganism with immunoregulatory properties, protected against the stress-induced reduction in systemic Tregs, increase in basal and LPS-induced in vitro splenocyte viability, as well as splenic in vitro GC resistance. Our findings further support the hypothesis that i.g. M. vaccae protects against CSC-associated splenic GC resistance via directly affecting the myeloid compartment, thereby preventing the CSC-induced upregulation of TLR4 in newly generated PMN-MDSCs. In contrast, the protective effects of i.g. M. vaccae on the CSC-induced upregulation of TLR2 in neutrophils and the subsequent increase in basal and LPS-induced in vitro splenocyte viability seems to be indirectly mediated via the Treg compartment. These data highlight the potential for use of oral administration of M. vaccae NCTC 11659 to prevent stress-induced exaggeration of inflammation, a risk factor for development of stress-related psychiatric disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Stress-associated somatic and psychiatric disorders are often linked to non-resolving low-grade inflammation, which is promoted at least in part by glucocorticoid (GC) resistance of distinct immune cell subpopulations. While the monocyte/macrophage compartment was in the focus of many clinical and preclinical studies, the role of myeloid-derived suppressor cells (MDSCs) in stress-associated pathologies and GC resistance is less understood. As GC resistance is a clear risk factor for posttraumatic complications in patients on intensive care, the exact interplay of physical and psychosocial traumatization in the development of GC resistance needs to be further clarified. In the current study we employ the chronic subordinate colony housing (CSC) paradigm, a well-characterized mouse model of chronic psychosocial stress, to study the role of myeloid cells, in particular of MDSCs, in innate immune activation and GC resistance following combined psychosocial and physical (e.g., bite wounds) trauma. Our findings support the hypothesis that stress-induced neutrophils, polymorphonuclear (PMN)-MDSCs and monocytes/monocyte-like (MO)-MDSCs get primed and activated locally in the bone marrow as determined by toll-like receptor (TLR)2 upregulation and increased basal and lipopolysaccharide (LPS)-induced in vitro cell viability. These primed and activated myeloid cells emigrate into the peripheral circulation and subsequently, if CSC is accompanied by significant bite wounding, accumulate in the spleen. Here, PMN-MDSCs and monocytes/MO-MDSCs upregulate TLR4 expression, which exclusively in PMN-MDSCs promotes NF-κB hyperactivation upon LPS-stimulation, thereby exceeding the anti-inflammatory capacities of GCs and resulting in GC resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The development of safe antimicrobial agents is important for the effective treatment of pathogens. From a multitude of discovered inhibitory compounds, only a few antimicrobial agents are able to enter the market. Many antimicrobials are, on the one hand, quite effective in killing pathogens but, on the other hand, cytotoxic to eukaryotic cells. Cell health can be monitored by various methods. Plasma membrane integrity, DNA synthesis, enzyme activity, and reducing conditions within the cell are known indicators of cell viability and cell death. For a comprehensive overview, methods to analyze cytotoxic and hemolytic effects, e.g., lactate dehydrogenase release, cell proliferation analysis, cell viability analysis based on the activity of different intracellular enzymes, and hemolysis assay of antimicrobial compounds on human cells, are described in this updated chapter., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

For more than 50years, hematopoietic stem cell transplantation (HSCT) has been the major curative therapy for hematological malignancies and genetic disorders, but its success is limited by the development of graft-versus-host disease (GVHD). GVHD represents a post-transplantation disorder representing the immune-mediated attack of transplant-derived T cells against recipient tissue finally leading to increased morbidity and mortality of the recipient. GVHD develops if donor and recipient are disparate in major or minor histocompatibility antigens (MHC, miHA). Most of the initial knowledge about the biology of GVHD is derived from murine bone marrow transplantation (BMT) models. Of course, GVHD mouse models do not reflect one to one the human situation, but they contribute significantly to our understanding how conditioning and danger signals activate the immune system, enlighten the role of individual molecules, e.g., cytokines, chemokines, death-inducing ligands, define the function of lymphocytes subpopulations for GVHD development and have significant impact on establishing new treatment and prevention strategies used in clinical HSCT. This chapter describes in detail the procedure of allogeneic BMT and the development of GVHD in two commonly used allogeneic murine BMT models (B6→B6.bm1, B6→B6D2F1) with different MHC disparities, which can be used as a basis for advanced studies of GVHD pathology or the development of new treatment strategies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells that dampen overwhelming adaptive immune responses through multiple mechanisms and are recognized as an attractive novel immune intervention therapy for counteracting the destructive effects of graft- versus -host disease (GVHD) developing after allogeneic bone marrow transplantation (BMT). MDSCs can be produced in great numbers for cellular therapy, but they present a mixture of subsets whose functions in GVHD prevention are undefined. Here, we generated MDSCs in vitro from murine BM cells in the presence of GM-CSF and defined the integrin CD11c as a marker to subdivide MDSCs into two functional subgroups: CD11b+CD11c+ and CD11b+CD11c- MDSCs. Isolated CD11b+CD11c+ and CD11b+CD11c- MDSCs both inhibited alloantigen-stimulated T-cell proliferation in vitro , although CD11b+CD11c+ MDSCs were more efficient and expressed higher levels of different immunosuppressive molecules. Likewise, expression of surface markers such as MHC class II, CD80, CD86, or PD-L1 further delineated both subsets. Most importantly, only the adoptive transfer of CD11b+CD11c+ MDSCs into a single MHC class I-disparate allogeneic BMT model prevented GVHD development and strongly decreased disease-induced mortality, while CD11b+CD11c- MDSCs were totally ineffective. Surprisingly, allogeneic T-cell homing and expansion in lymphatic and GVHD target organs were not affected by cotransplanted CD11b+CD11c+ MDSCs indicating a clear contradiction between in vitro and in vivo functions of MDSCs. However, CD11b+CD11c+ MDSCs shifted immune responses towards type 2 immunity reflected by increased Th2-specific cytokine expression of allogeneic T cells. Induction of type 2 immunity was mandatory for GVHD prevention, since CD11b+CD11c+ MDSCs were ineffective if recipients were reconstituted with STAT6-deficient T cells unable to differentiate into Th2 cells. Most importantly, the beneficial graft- versus -tumor (GVT) effect was maintained in the presence of CD11b+CD11c+ MDSCs since syngeneic tumor cells were efficiently eradicated. Strong differences in the transcriptomic landscape of both subpopulations underlined their functional differences. Defining CD11b+CD11c+ MDSCs as the subset of in vitro -generated MDSCs able to inhibit GVHD development might help to increase efficiency of MDSC therapy and to further delineate relevant target molecules and signaling pathways responsible for GVHD prevention., Competing Interests: KK, HH, KF-C, and SP are employed by Boehringer Ingelheim Pharma Co. KG and Boehringer Ingelheim RCV GmbH & Co. KG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scheurer, Kitt, Huber, Fundel-Clemens, Pflanz, Debatin and Strauss.)

The immunosuppressant rapamycin (RAPA) inhibits mammalian target of rapamycin (mTOR) functions and is applied after allogeneic bone marrow transplantation (BMT) to attenuate the development of graft-versus-host disease (GVHD), although the cellular targets of RAPA treatment are not well defined. Allogeneic T cells are the main drivers of GVHD, while immunoregulatory myeloid-derived suppressor cells (MDSCs) were recently identified as potent disease inhibitors. In this study, we analyzed whether RAPA prevents the deleterious effects of allogeneic T cells or supports the immunosuppressive functions of MDSCs in a BMT model with major histocompatibility complex (MHC) classes I and II disparities. RAPA treatment efficiently attenuated clinical and histological GVHD and strongly decreased disease-induced mortality. Although splenocyte numbers increased during RAPA treatment, the ratio of effector T cells to MDSCs was unaltered. However, RAPA treatment induced massive changes in the genomic landscape of MDSCs preferentially up-regulating genes responsible for uptake or signal transduction of lipopeptides and lipoproteins. Most importantly, MDSCs from RAPA-treated mice exhibited increased immunosuppressive potential, which was primarily inducible nitric oxide synthase (iNOS)-dependent. Surprisingly, RAPA treatment had no impact on the genomic landscape of T cells, which was reflected by unchanged expression of activation and exhaustion markers and cytokine profiles in T cells from RAPA-treated and untreated mice. Similarly, T cell cytotoxicity and the graft-versus-tumor effect were maintained as co-transplanted tumor cells were efficiently eradicated, indicating that the immunosuppressant RAPA might be an attractive approach to strengthen the immunosuppressive function of MDSCs without affecting T cell immunity., (© 2020 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)

Good public transport accessibility is associated with active travel, but this is under-researched among adolescents. We tested associations between public transport accessibility and active travel among school-going adolescents (12-18 years; n = 1329) from Melbourne, Australia analysing Victorian Integrated Survey of Travel and Activity data. Outcomes included main mode of transport to school and accumulating ≥20 min of active travel over the day. Low and high compared to no public transport accessibility around homes were associated with higher odds of public transport use (low (odds ratio (OR): 1.94 95% confidence interval (CI): 1.28, 2.94) high (OR: 2.86 95% CI: 1.80, 4.53)). Low and high public transport accessibility around homes were also associated with higher prevalence of achieving ≥20 min of active travel (low (prevalence ratio (PR): 1.14 95% CI: 0.97, 1.34) high (PR: 1.31 95% CI: 1.11, 1.54)) compared to none. Public transport accessibility around schools was associated with public transport use (low (OR: 2.13 95% CI: 1.40, 3.24) high (OR: 5.07 95% CI: 3.35, 7.67)) and achieving ≥20 min of active travel (low (PR: 1.18 95% CI: 1.00, 1.38) high (PR: 1.64 95% CI: 1.41, 1.90)). Positive associations were confirmed between public transport accessibility and both outcomes of active travel.

Background: Physical inactivity is a global public health problem, partly due to urbanization and increased use of passive modes of transport such as private motor vehicles. Improving accessibility to public transport could be an effective policy for Governments to promote equity and efficiency within transportation systems, increase population levels of physical activity and reduce the negative externalities of motor vehicle use. Quantitative estimates of the health impacts of improvements to public transport accessibility may be useful for resource allocation and priority-setting, however few studies have been published to inform this decision-making. This paper aims to estimate the physical activity, obesity, injury, health and healthcare cost-saving outcomes of scenario-based improvements to public transport accessibility in Melbourne, Australia., Methods: Baseline and two hypothetical future scenario estimates of improved public transport accessibility for Melbourne, Australia, were derived using a spatial planning and decision tool designed to simulate accessibility performance (the Spatial Network Analysis for Multimodal Urban Transport Systems (SNAMUTS)). Public transport related physical activity was quantified by strata of age group and sex from Melbourne travel survey data (VISTA survey) and used with the SNAMUTS Composite Index to estimate input data for health impact modelling for the Melbourne population aged 20-74 years. A proportional multi-state, multiple cohort lifetable Markov model quantified the potential health gains and healthcare cost-savings from estimated changes in physical activity, body weight and injuries related to walking to access/egress public transport under two scenarios: (S1) public transport accessibility under current policy directions, and (S2) multi-directional, high-frequency network improvements., Results: Multi-directional, high-frequency improvements to the public transport network (S2) resulted in significantly greater health and economic gains than current policy directions (S1) in relation to physical activity (mean 6.4 more MET minutes/week), body weight (mean 0.05 kg differential), health-adjusted life years gained (absolute difference of 4878 HALYs gained) and healthcare cost-savings (absolute difference of AUD43M), as compared to business as usual under both scenarios (n = 2,832,241 adults, over the lifecourse)., Conclusions: Based on our conservative analyses, improving accessibility to public transport will improve population health by facilitating physical activity and lead to healthcare cost savings compared with business-as-usual. These wider health benefits should be better considered in transport planning and policy decisions.

Background: Most research on walking for transport has focused on the walkability of residential neighborhoods, overlooking the contribution of places of work/study and the ease with which destinations outside the immediate neighborhood can be accessed, referred to as regional accessibility., Objectives: We aimed to examine if local accessibility/walkability around place of work/study and regional accessibility are independently and interactively associated with walking., Methods: A sample of 4,913 adult commuters was derived from a household travel survey in Melbourne, Australia (2012-2014). Local accessibility was measured as the availability of destinations within an 800 - m pedestrian network from homes and places of work/education using a local living index [LLI; 0-3 (low), 4-6, 7-9, and 10-12 (high) destinations]. Regional accessibility was estimated using employment opportunity, commute travel time by mode, and public transport accessibility. Every individual's potential minutes of walking for each level of exposure (observed and counter to fact) were predicted using multivariable regression models including confounders and interaction terms. For each contrast of exposure levels of interest, the corresponding within-individual differences in predicted walking were averaged across individuals to estimate marginal effects., Results: High LLI at home and work/education was associated with more minutes walking than low LLI by 3.9 [95% confidence interval (CI): 2.3, 5.5] and 8.3 (95% CI: 7.3, 9.3) min, respectively, in mutually adjusted models. Across regional accessibility measures, an independent association with walking and an interactive association with LLI at work/education was observed. To take one example, the regional accessibility measure of "Jobs within 30 min by public transport" was associated with 4.3 (95% CI: 2.9, 5.7) more mins walking for high ( ≥ 30,000   jobs ) compared with low ( < 4,000   jobs ) accessibility in adjusted models. The estimated difference for high vs. low LLI (work/education) (among those with low regional accessibility) was 3.6 min (95% CI: 2.3, 4.8), while the difference for high vs. low regional accessibility (among those with low LLI) was negligible ( - 0.01 ; 95% CI: - 1.2 , 1.2). However, the combined effect estimate for high LLI and high regional accessibility, compared with low on both, was 12.8 min (95% CI: 11.1, 14.5), or 9.3 (95% CI: 6.7, 11.8) min/d walking more than expected based on the separate effect estimates., Conclusions: High local living (work/education) and regional accessibility, regardless of the regional accessibility measure used, are positively associated with physical activity. High exposure to both is associated with greater benefit than exposure to one or the other alone. https://doi.org/10.1289/EHP3395.

Objective: Physical activity (PA) during pregnancy is associated with lower neonatal fat mass, but associations with child body composition are mixed. The purpose of this study was to examine associations between trimester-specific pregnancy PA and child body composition at 4 years., Methods: Participants of the Minnesota Infant Nutrition, Neurodevelopment, and Obesity Study were asked to recall participation in any moderate or vigorous PA in the first (T1), second (T2) and third (T3) trimesters at about 5 years postpartum. Child fat mass and fat-free mass were measured via air displacement plethysmography at 2 weeks, 3 months and 4 years of age. Multivariate linear regression was used for analyses., Results: Of 51 possible participants, 37 recalled pregnancy PA. Any vigorous PA in T3 was associated with lower child fat mass at 4 years (adj β  = -1.077, p  < 0.05)., Conclusion: Late pregnancy PA may have lasting benefits for child body composition. Replication of these findings is needed in a larger sample with prospective measures., Competing Interests: The authors report no conflicts of interest.

New rotational bands built on the ν(h&#95;{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

A body of a 91-year-old donor underwent whole-body CT scanning before being transferred for use in an anatomical dissection course. Metallic objects were detected in the thigh muscles, extensive bone abnormalities were found in the left femur and the diaphysis of the left femur was 50% wider than that of the right diaphysis. History revealed that the body donor had been seriously wounded at the end of World War II by a rocket explosion. His multiple fractures and lesions had not been surgically treated either in an Austrian military hospital or in a French prisoner of war camp. The patient suffered for almost 70 years from this violation of the Geneva Conventions. In the light of current armed conflicts, the present case is an example of how one injustice can result in severe, lifelong medical consequences. It also shows that the history behind a wounded thigh can have an enormous impact on teaching ethics to today's medical students., (2016 BMJ Publishing Group Ltd.)

Objective: Characterize the relationship between neonatal hyperglycemia and growth and body composition at 4 months corrected age (CA) in very low birth weight (VLBW) preterm infants., Study Design: A prospective study of VLBW appropriate-for-gestation infants (N=53). All blood glucose measurements in the first 14 days and nutritional intake and illness markers until discharge were recorded. Standard anthropometrics and body composition via air displacement plethysmography were measured near term CA and 4 months CA. Relationships between hyperglycemia and anthropometrics and body composition were examined using multivariate linear regression., Results: Infants with >5 days of hyperglycemia were lighter (5345 vs 6455 g, P⩽0.001), shorter (57.9 vs 60.9 cm, P⩽0.01), had smaller occipital-frontal head circumference (39.4 vs 42.0 cm, P⩽0.05) and were leaner (percent body fat 15.0 vs 23.8, P⩽0.01) at 4 months CA than those who did not have hyperglycemia, including after correcting for nutritional and illness factors., Conclusions: Neonatal hyperglycemia in VLBW infants is associated with decreased body size and lower adiposity at 4 months CA independent of nutritional deficit, insulin use and illness. Downregulation of the growth hormone axis may be responsible. These changes may influence long-term growth and cognitive development.

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

Fast adiabatic plasma heating of a thin solid target irradiated by a high intensity laser has been observed by an optical fast interferometry diagnostic. It is driven by the hot electron current induced by the laser plasma interaction at the front side of the target. Radial and longitudinal temperature profiles are calculated to reproduce the observed rear-side plasma expansion. The main parameters of the suprathermal electrons (number, temperature, and divergence) have been deduced from these observations.

We present a protocol to characterize the high energy electron beam emitted in the interaction of an ultraintense laser with matter at intensities higher than 10(19) W cm(-2). The electron energies and angular distributions are determined as well as the total number of electrons produced above a 10 MeV threshold. This protocol is based on measurements with an electron spectrometer and nuclear activation techniques, combined with Monte Carlo simulations based on the GEANT3 code. The method is detailed and exemplified with data obtained with polypropylene and copper thin solid targets at a laser intensity of 2x10(19) W cm(-2). Special care is taken of the different sources of uncertainties. In particular, the reproducibility of the laser shots is considered.

We report on strong nonuniformities in target heating with intense, laser-produced proton beams. The observed inhomogeneity in energy deposition can strongly perturb equation of state (EOS) measurements with laser-accelerated ions which are planned in several laboratories. Interferometric measurements of the target expansion show different expansion velocities on the front and rear surfaces, indicating a strong difference in local temperature. The nonuniformity indicates at an additional heating mechanism, which seems to originate from electrons in the keV range.

Energy and angular distributions of the fast outgoing electron beam induced by the interaction of a 1 J, 30 fs, 2 x 10(19) W/cm(2), 10 Hz laser with a thin foil target are characterized by electron energy spectroscopy and photonuclear reactions. We have investigated the effect of the target thickness and the intensity contrast ratio level on the electron production. Using a 6-microm polyethylene target, up to 4 x 10(8) electrons with energies between 5 and 60 MeV were produced per laser pulse and converted to gamma rays by bremsstrahlung in a Ta secondary target. The rates of photofission of U as well as photonuclear reactions in Cu, Au, and C samples have been measured. In optimal focusing conditions, about 0.06% of the laser energy has been converted to outgoing electrons with energies above 5 MeV. Such electrons leave the target in the laser direction with an opening angle of 2.5 degrees.

Plasmas are an attractive medium for the next generation of particle accelerators because they can support electric fields greater than several hundred gigavolts per meter. These accelerating fields are generated by relativistic plasma waves-space-charge oscillations-that can be excited when a high-intensity laser propagates through a plasma. Large currents of background electrons can then be trapped and subsequently accelerated by these relativistic waves. In the forced laser wake field regime, where the laser pulse length is of the order of the plasma wavelength, we show that a gain in maximum electron energy of up to 200 megaelectronvolts can be achieved, along with an improvement in the quality of the ultrashort electron beam.

We have measured the cross section of the 7Be(p,gamma)8B reaction for E(c.m.) = 185.8, 134.7, and 111.7 keV using a radioactive 7Be target (132 mCi). Single and coincidence spectra of beta+ and alpha particles from 8B and 8Be* decay, respectively, were measured using a large acceptance spectrometer. The zero energy S factor inferred from these data is 18.5+/-2.4 eV b and a weighted mean value of 18.8+/-1.7 eV b (theoretical uncertainty included) is deduced when combining this value with our previous results at higher energies.

Background: In 1990 the Haemophilus influenzae b-Diphtheria conjugate vaccine (Hib-D) was introduced in Germany. In addition, most children under 18 months of age failed to develop protective levels of Hib antibodies in response to systemic infections., Methods: To evaluate the protective efficacy of the Hib-D vaccine in Germany a post marketing case-control study was performed during 1.5. 1990-30.4. 1992. Surveillance for invasive Hib-infections was maintained by pediatricians of 8 hospitals in the Rhein-Main area. The antibody responses to Hib were evaluated by ELISA at the onset (days 0-3) and during remission of disease., Results: During the first year of the study 23 cases per 100,000 children of invasive Hib-infections were recorded. Of these children, 15 suffered from meningitis, 6 from epiglottitis and one from cellulitis and pericarditis respectively. None of these patients had been vaccinated except for one, who received two injections of Hib-D. Due to increased acceptance of the Hib-D vaccine we found a significant reduction of invasive Hib-infections (6 cases per 100,000 children) in the second year of the study. Again, of these children only one child was vaccinated. As expected, in all patients investigated the initial Hib antibody level was below 1 microgram/ml. The development of Hib specific immunity to invasive disease was clearly age dependent: 10 of 11 children below 18 months failed to produce any Hib antibodies (> 0.15 microgram/ml) in response to their infection. In contrast 8 of 10 children older than 18 months developed protective antibody levels to Hib., Conclusions: The incidence of serious Hib-disease has significantly decreased in Germany since the introduction of the Hib-D vaccine. Because no other Hib vaccine was licensed in Germany our data confirm efficacy and safety of Hib-D reported previously. In addition, children, who contracted disease before 18 months of age, remain susceptible to Hib and require active immunization for protection.

Solid-phase extraction procedures are being used increasingly in all types of drug testing laboratories, including those which carry out forensic toxicology. The advantages of such procedures include decreased operator time, reduced solvent volumes, and increased extraction efficiency. The application of existing techniques, however, has not yet been applied to tissues that are widely available postmortem. Tissue analysis can make the task of interpretation of drug levels much easier, particularly where unstable drugs are involved (e.g., cocaine). This review article explores the possibilities of applying existing extraction procedures to human tissue samples. We also consider the reasons why forensic laboratories have been slow to investigate such possibilities. We hope to stimulate interest in alternative tissue extraction procedures by reviewing reported procedures that apply to both human and animal tissue.

A rapid procedure is described for the extraction and analysis of brain samples for cocaine and benzoylecgonine. Human brain tissue was sectioned at autopsy, and samples were subjected to a lipase digestion, subsequent to solid-phase extraction. The distribution of cocaine and benzoylecgonine throughout different regions of the brain was determined by high-performance liquid chromatography.

The authors review the development and the controversies of the neuroleptic threshold theory. According to this theory, the minimum effective antipsychotic dose of a neuroleptic ("threshold dose") correlates with the appearance of "fine motor" symptoms (micrography) as opposed to the appearance of manifest or "coarse motor" extrapyramidal side effects. About half of the acutely exacerbated schizophrenic patients respond to threshold doses, but no predictors are known to characterize the responders. The neuroleptic threshold doses were found to be low, and the low dose treatment strategy is supported by the results of current PET and neuroleptic plasma level studies.

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T 0/2, N 0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitive methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical "thymus dependent") area; volume of the follicular (predominantly B-cell) cortex and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded marcrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinushistiocytosis) correlated inversely with survival. Besides the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T1/2, N0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients, 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitative methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical ("thymus-dependent") area; volume of the follicular (predominantly B-cell) cortex; and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded macrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinuhistiocytosis) correlated inversely with survival. In addition to the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.