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The LUX-ZEPLIN (LZ) experiment is a dual-phase xenon time project chamber operating in the Sanford Underground Research Facility in South Dakota, USA. We report on the results of a relativistic extension to the nonrelativistic effective field theory (NREFT) from a 5.5 t fiducial mass and 60 live days of exposure. We present constraints on couplings from covariant interactions arising from the coupling of vector, axial currents, and electric dipole moments of the nucleon to the magnetic and electric dipole moments of the weakly interacting massive particle which cannot be described by recasting previous results described by an NREFT. Using a profile-likelihood ratio analysis, in an energy region between 0  keV_{nr} to 270  keV_{nr}, we report 90% confidence level exclusion limits on the coupling strength of five interactions in both the isoscalar and isovector bases.

The field of vascularized composite allograft (VCA) transplantation has seen steady, rapid growth, with new innovations driving the evolution from experimental procedures to more standardized therapies. With this expansion comes challenges with graft allocation, preservation, and postoperative graft rejection. Here, we outline the first example of subzero nonfreezing (SZNF), supercooled storage of a whole rat hindlimb with orthotopic transplantation. Rat hindlimbs were procured, loaded, and supercooled for 48 hours at -4°C (n = 4), after which, they were recovered. The loading and recovery phase were performed using subnormothermic machine perfusion (SNMP) during which viability markers (glucose and oxygen consumption, lactate, and resistance) were tracked. Control limbs underwent static cold storage (SCS). After ex vivo validation, the model was piloted in a transplant model, comparing 48 hours of SZNF (n = 1), 48 hours of SCS (n = 1), and 72 hours of SCS (n = 1), which demonstrated no survival beyond postoperative day 4 in the SCS models, and survival until the end of study (postoperative day [POD] 28) in the SZNF model. This study demonstrates the promise of this model in future studies on long-term VCA preservation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KU reports a relationship with Sylvatica Biotech Inc that includes: board membership and equity or stocks. BEU reports a relationship with Sylvatica Biotech Inc that includes: equity or stocks. KU has a patent issued to MGH. KUun has patent pending to MGH. BEU has a patent issued to MGH. IFvR has a patent pending to MGH. MST, MEM, ATD, JHC, and ABMvdM 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 © 2024 Elsevier Inc. All rights reserved.)

Full-spectrum flow cytometry has increased antibody-based multiplexing, yet further increases remain potentially impactful. We recently proposed how fluorescence multiplexing using spectral imaging and combinatorics (MuSIC) could do so using tandem dyes and an oligo-based antibody labeling method. In this work, we found that such labeled antibodies had significantly lower signal intensities than conventionally labeled antibodies in human cell experiments. To improve signal intensity, we tested moving the fluorophores from the original external (ext.) 5' or 3' end-labeled orientation to internal (int.) fluorophore modifications. Cell-free spectrophotometer measurements showed a ∼6-fold signal intensity increase of the new int. configuration compared to the previous ext. configuration. Time-resolved fluorescence and fluorescence correlation spectroscopy showed that the ∼3-fold brightness difference is due to static quenching most likely by the oligo or solution in the ext. configuration. Spectral flow cytometry experiments using peripheral blood mononuclear cells show int. MuSIC probe-labeled antibodies (i) retained increased signal intensity while having no significant difference in the estimated % of CD8+ lymphocytes and (ii) labeled with Atto488, Atto647, and Atto488/647 combinations can be demultiplexed in triple-stained samples. The antibody labeling approach is general and can be broadly applied to many biological and diagnostic applications where spectral detection is available.

Objective: To develop and psychometrically evaluate an adapted version of the Female Self-Advocacy in Cancer Survivorship (FSACS) Scale in men with a history of cancer., Methods: This psychometric instrument development and validation study used a two-phase approach to first adapt the FSACS Scale items to reflect the experience of men with a history of cancer and then evaluate the psychometric properties of the adapted scale compared to the original FSACS Scale. The study was conducted from December 2018 through April 2022 through cancer clinics, patient registries, and national advocacy organizations. We evaluated scale reliability and validity using reliability coefficients, exploratory and confirmatory factor analyses, and item analyses to determine a final set of scale items., Results: Item responses from N = 171 men with a history of cancer were evaluated to determine scale validity. After removing poor-performing items based on item-level analyses, factor analyses confirmed that a 3-factor structure of both the adapted and original FSACS Scale best fit the scale. The 10 new items did not outperform the original 20-item scale and were therefore excluded from the final scale. The final 20-item scale explained 87.94% of item variance and subscale's Cronbach α varied from 0.65 to 0.86., Conclusion: The SACS Scale can be used in research and clinical contexts to assess the propensity of men and women to get their needs, values, and priorities met in the face of a challenge., (© 2023 John Wiley & Sons Ltd.)

Systematic, genome-scale genetic screens have been instrumental for elucidating genotype-phenotype relationships, but approaches for probing genetic interactions have been limited to at most ∼100 pre-selected gene combinations in mammalian cells. Here, we introduce a theory for high-throughput genetic interaction screens. The theory extends our recently developed Multiplexing using Spectral Imaging and Combinatorics (MuSIC) approach to propose ∼10 5 spectrally unique, genetically encoded MuSIC barcodes from 18 currently available fluorescent proteins. Simulation studies based on constraints imposed by spectral flow cytometry equipment suggest that genetic interaction screens at the human genome-scale may be possible if MuSIC barcodes can be paired to guide RNAs. While experimental testing of this theory awaits, it offers transformative potential for genetic perturbation technology and knowledge of genetic function. More broadly, the availability of a genome-scale spectral barcode library for non-destructive identification of single cells could find more widespread applications such as traditional genetic screening and high-dimensional lineage tracing.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9  GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36  GeV/c^{2}, rejecting cross sections above 9.2×10^{-48}  cm at the 90% confidence level.

Objectives: To determine whether socioeconomic status (SES) and small birthweight for gestational age (SGA) exhibit independent or joint effects on infant levels of 42 metabolites., Study Design: Population-based retrospective cohort of metabolic newborn screening information linked to hospital discharge data. SGA infants defined by birthweight <10th percentile for gestational age by sex. SES was determined by a combined metric including education level, participation in the WIC nutritional assistance program, and receiving California MediCal insurance. We performed linear regression to determine the effects of SES independently, SGA independently, and the interaction of SGA and SES on 42 newborn metabolite levels., Results: 736,435 California infants born in 2005-2011 were included in the analysis. SGA was significantly associated with 36 metabolites. SES was significantly associated with 41 of 42 metabolites. Thirty-eight metabolites exhibited a dose-response relationship between SGA and metabolite levels as SES worsened. Fourteen metabolites showed significant interaction between SES and SGA. Eight metabolites showed significant individual and joint effects of SES and SGA: alanine, glycine, free carnitine, C-3DC, C-5DC, C-16:1, C-18:1, and C-18:2., Conclusions: SES and SGA exhibited independent effects on a majority of metabolites and joint effects on select metabolites. A better understanding of how SES and SGA status are related to infant metabolites may help identify maternal and newborn interventions that can lead to better outcomes for infants born SGA.

Multiangle light scattering (MALS) was used to determine the absolute molar mass of fluorescent macromolecules. It is standard protocol to install bandwidth filters before MALS detectors to suppress detection of fluorescent emissions. Fluorescence can introduce tremendous error in light scattering measurements and is a formidable challenge in accurately characterizing fluorescent macromolecules and particles. However, we show that for some systems, bandwidth filters alone are insufficient for blocking fluorescence in molar mass determinations. For these systems, we have devised a correction procedure to calculate the amount of fluorescence interference in the filtered signal. By determining the intensity of fluorescent emission not blocked by the bandwidth filters, we can correct the filtered signal accordingly and accurately determine the true molar mass. The transmission rates are calculated before MALS experimentation using emission data from standard fluorimetry techniques, allowing for the characterization of unknown samples. To validate the correction procedure, we synthesized fluorescent dye-conjugated proteins using an IR800CW (LI-COR) fluorophore and Bovine Serum Albumin protein. We successfully eliminated fluorescence interference in MALS measurements using this approach. This correction procedure has potential application toward more accurate molar mass characterizations of macromolecules with intrinsic fluorescence, such as lignins, fluorescent proteins, fluorescence-tagged proteins, and optically active nanoparticles.

Fluorescent antibodies are a workhorse of biomedical science, but fluorescence multiplexing has been notoriously difficult due to spectral overlap between fluorophores. We recently established proof-of-principal for fluorescence Multiplexing using Spectral Imaging and Combinatorics (MuSIC), which uses combinations of existing fluorophores to create unique spectral signatures for increased multiplexing. However, a method for labeling antibodies with MuSIC probes has not yet been developed. Here, we present a method for labeling antibodies with MuSIC probes. We conjugate a DBCO-Peg5-NHS ester linker to antibodies and a single-stranded DNA "docking strand" to the linker and, finally, hybridize two MuSIC-compatible, fluorescently labeled oligos to the docking strand. We validate the labeling protocol with spin-column purification and absorbance measurements. We demonstrate the approach using (i) Cy3, (ii) Tex615, and (iii) a Cy3-Tex615 combination as three different MuSIC probes attached to three separate batches of antibodies. We created single-, double-, and triple-positive beads that are analogous to single cells by incubating MuSIC probe-labeled antibodies with protein A beads. Spectral flow cytometry experiments demonstrate that each MuSIC probe can be uniquely distinguished, and the fraction of beads in a mixture with different staining patterns are accurately inferred. The approach is general and might be more broadly applied to cell-type profiling or tissue heterogeneity studies in clinical, biomedical, and drug discovery research.

Objectives: To assess outcomes for Veterans Health Administration (VHA) patients following calls to the Veterans Crisis Line (VCL)., Methods: 158,927 VHA patients had an initial VCL call in 2010-2015 with documented identifiers. Multivariable proportional hazards regressions assessed risks of suicide and suicide-related behavior through 12 months. Covariates included age, sex, region, mental health encounters in the prior year, time of day, weekday/weekend status, call outcome, and responder determination of caller risk., Results: Annualized suicide rates per 100,000 within 1, 3, 6, and 12 months were 797, 520, 387, and 298, respectively. Average age was 49.9 (SD = 15.2), 86.5% were male, 68.6% received mental health encounters in the prior year, and 5.9% had calls categorized as at high risk. Adjusting for covariates, suicide risk was greater among male callers and those with calls categorized as at high or moderate risk., Conclusions: Veterans Crisis Line serves a high-risk population at a critical time. Rates were particularly high within one month and remained substantially elevated through 12 months. Findings have directly informed ongoing efforts to enhance coordination between VCL and VHA to support suicide prevention., (© Published 2020. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Water and wastewater utilities, water and sanitation hygiene (WASH) practitioners, and regulating bodies, particularly in developing nations, rely heavily on indicator microorganisms, as opposed to pathogens, for much of their regulatory decisions. This commentary illustrates the importance of considering pathogens and not relying only on indicator organisms when making decisions regarding water and sanitation, especially with respect to meeting the current targets of the Sustainable Development Goal (SDG) 6. We use quantitative microbial risk assessment (QMRA) to present three common scenarios that WASH and public health practitioners encounter to illustrate our point. These include 1) chlorination of surface water for drinking, 2) land application of latrine waste as a fertilizer, and 3) recreation/domestic use of surface waters impacted by wastewater discharge. We show that the calculated probabilities of risk of infection are statistically significantly higher when using treatment/survival information for pathogens versus using indicator species data. Thus, demonstrating that relying solely on indicators for sanitation decision making is inadequate if we truly want to achieve the SDG6 targets of safely managed water and sanitation services., 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 © 2020. Published by Elsevier Ltd.)

Based on an analysis of relevant laws and policies, regulator data portals, and information requests, we find that clinical data, including clinical study reports, submitted to the European Medicines Agency and Health Canada to support approval of medicines are routinely made publicly available.

Background: Precise flap planning and perforator selection are paramount for successful perforator flap surgery. Portable color-flow ultrasound (PCFU) is a convenient, low-cost, easily accessible imaging modality that is pivotal in the planning of perforator flaps where anatomic variability is the rule., Methods: Perforator mapping was performed using an L12-4 linear-array ultrasound probe connected to an Android tablet. Images were obtained with the Lumify app (Philips Lumify, usa.philips.com). Perforator characteristics were recorded (arterial diameter, emergence points from fascia, subcutaneous course, and projection onto the skin surface) using still images and real-time videos., Results: Thirty consecutive patients had 40 perforator or musculocutaneous flap reconstructions over a 2-year period. For the 15 flaps that had preoperative computed tomographic angiography (CTA) imaging, the preoperative sonographic measurements correlated with CTA and intraoperative findings. Portable color-flow ultrasound allowed perforator flap design and selection based on the largest available perforator, the most appropriate flap thickness, and comparison of multiple donor sites including left versus right. Two deep inferior epigastric perforator patients required take-back to the operating room for debridement of devitalized nonflap tissue. The superior gluteal artery perforator flap was abandoned intraoperatively due to proximal vascular anomalies. Overall flap success rate was 98% (39/40 flaps)., Conclusions: Our experience with PCFU has rapidly improved, allowing individualized perforator flap selection and design based on each patient's unique perforator anatomy, reconstructive requirements, and donor site characteristics. In our practice, PCFU has supplemented CTA and in many cases has supplanted CTA as the primary imaging modality of choice in the planning of perforator flap reconstruction.

Background: The demand for body contouring surgery continues to rise. The inclusion of the superficial fascial system (SFS) during closure of such procedures has been shown to improve outcomes; however, currently reported wound complication rates remain high. The authors assess whether decreased quantities of SFS are associated with wound complications in these patients., Methods: A retrospective study of patients undergoing body contouring surgery was performed. Preoperatively, ultrasound images were obtained of the SFS. Using Cellprofiler, the mean gray values (MGVs) of the SFS were calculated to quantify this structure. Chart review was performed to identify postoperative wound complications., Results: Thirty-six patients were included: 30 abdominoplasties, 3 bilateral medial thigh lifts, and 3 bilateral brachioplasties. The overall wound complication rate was 22.5%. There were no significant differences in body mass index, age, smoking status, weight of resected specimen, or diabetes when comparing the complication and noncomplication groups. However, the MGV was significantly greater in the noncomplication group compared with the complication group (0.135 ± 0.008 vs 0.099 ± 0.005, respectively, P = 0.03). The average MGV for the entire cohort was 0.127. Patients with an MGV of greater than 0.127 had a wound complication rate of 0% compared with that of 39% for patients with an MGV of 0.127 or less (P = 0.005)., Conclusions: Poor quantities of SFS identified by ultrasound were associated with increased wound complications in patients undergoing body contouring surgery. Furthermore, patients with better than average SFS seem to be protected from such complications.

Background: This study is the first to correlate sonographic findings of subcutaneous tissue to structural and biomechanical properties., Methods: Precisely sized tissue specimens (59 samples) were collected from five abdominoplasty procedures. A Philips Lumify L12-4 linear array probe, connected to an Android tablet, was used to obtain ultrasound images of the superficial fascial system. A no. 1 Vicryl suture on a CTX needle placed though a needle guide within a three-dimensionally printed template ensured equal bites of subcutaneous tissue across specimens. Suture pull-out strength was measured until failure at a displacement rate of 2.12 mm/second using an Admet MTEST Quattro. Mean gray value for the superficial fascial system in associated ultrasonographic images was quantified by CellProfiler., Results: Superficial fascial system visualization can be accomplished using high-resolution portable ultrasound. Comparing multiple specimens' imaging, interpatient and intrapatient variability of superficial fascial system quantity and structural characteristics are apparent. The superficial fascial system is highly abundant in some patients, but has limited presence in others. Individual-specimen mean gray value and whole-patient mean gray value positively correlated with tissue tensile strength (p = 0.006) and patient-average tissue tensile strength (p = 0.036), respectively. Whole-patient mean gray value accounted for 98.5 percent of the variance seen in patient-average tensile strength, making it a strong predictor for tensile strength., Conclusions: Portable ultrasound and image-processing technology can visualize, quantify, and predict subcutaneous tissue strength of the superficial fascial system. The superficial fascial system quantity correlates with suture tensile strength. Clinically, preoperative superficial fascial system quantification may aid in outcome predictions, manage patient expectations, and potentially lower complication rates., Clinical Question/level of Evidence: Diagnostic, V.

Our objective was to assess the relationship between hyperbilirubinemia with and without kernicterus and metabolic profile at newborn screening. Included were 1,693,658 infants divided into a training or testing subset in a ratio of 3:1. Forty-two metabolites were analyzed using logistic regression (odds ratios (ORs), area under the receiver operating characteristic curve (AUC), 95% confidence intervals (CIs)). Several metabolite patterns remained consistent across gestational age groups for hyperbilirubinemia without kernicterus. Thyroid stimulating hormone (TSH) and C-18:2 were decreased, whereas tyrosine and C-3 were increased in infants across groupings. Increased C-3 was also observed for kernicterus (OR: 3.17; 95% CI: 1.18-8.53). Thirty-one metabolites were associated with hyperbilirubinemia without kernicterus in the training set. Phenylalanine (OR: 1.91; 95% CI: 1.85-1.97), ornithine (OR: 0.76; 95% 0.74-0.77), and isoleucine + leucine (OR: 0.63; 95% CI: 0.61-0.65) were the most strongly associated. This study showed that newborn metabolic function is associated with hyperbilirubinemia with and without kernicterus., (© 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Streams are being subjected to physical, chemical, and biological stresses stemming from both natural and anthropogenic changes to the planet. In the face of limited time and resources, scientists, resource managers, and policy makers need ways to rank stressors and their impacts so that we can prioritize them from the most to least important (i.e., perform 'ecological triage'). We report results from an experiment in which we established a periphyton community from the Huron River (Michigan, USA) in 84 experimental 'flumes' (stream mesocosms). We then dosed the flumes with gradients of six common stressors (increased temperature, taxa extinctions, sedimentation, nitrogen, phosphorus, and road salt) and monitored periphyton structure and function. A set of a priori deterministic functions were fit to each stressor-endpoint response and model averaging based on AICc weights was used to develop concentration-response best-fit predictions. Model predictions from different stressors were then compared to forecasts of future environmental change to rank stressors according to the potential magnitude of impacts. All of the stressors studied altered at least one characteristic of the periphyton; however, the extent (i.e., structural and functional changes) and magnitude of effects expected under future forecasts differed significantly among stressors. Elevated nitrogen concentrations are projected to have the greatest combined effect on stream periphyton structure and function. Extinction, sediment, and phosphorus all had similar but less substantial impact on the periphyton (e.g., affected only structure not function, smaller magnitude change). Elevated temperature and salt both had measurable effects on periphyton, but their overall impacts were much lower than any of the other stressors. For periphyton in the Huron River, our results suggest that, among the stressors examined, increased N pollution may have the greatest potential to alter the structure and function of the periphyton community, and managers should prioritize reducing anthropogenic sources of nitrogen. Our study demonstrates an experimental approach to ecological triage that can be used as an additional line of evidence to prioritize management decisions for specific ecosystems in the face of ecological change., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KJK is employed by a commercial consulting company Exponent. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

We introduce a closed form equation, validated by simulations and experimental results that predicts the residual nonlinear noise ratio in mid-link OPC assisted discretely amplified systems. The model anticipates the reduction in performance enhancement achieved by mid-link OPC as the bandwidth of the modulated signals increases. The numerical analysis shows that uncompensated signal-signal interactions limit the performance improvement achieved by the introduction of additional OPCs. The numerical analysis predicts that the deployment of shorter amplifier spacing will lead to a greater performance enhancement. The numerical results are validated by experimentally testing of 2x, 4x, and 8x28Gbaud PM-QPSK systems with mid-link OPC compensation in a discretely amplified system with 100km amplifier spacing. The experimentally obtained reach enhancement (43%, 32%, and 24% for 2x28Gbaud, 4x28Gbaud, and 8x28Gbaud, respectively) confirms that the compensation efficiency of mid-link OPC is highly dependent on the number of channels (bandwidth) propagating along the system.

We experimentally demonstrate nonlinear noise compensation in an optical phase conjugation assisted 1 st order Raman amplified 30x30Gbaud DP-QPSK transmission system with a spectral efficiency of 3.6b/s/Hz. We show that by optimizing the link symmetry, even with only 1 st order Raman amplification a single, mid-link, optical phase conjugation compensates for 90% of the signal-signal nonlinear interference resulting in a 2.3dB performance enhancement. We show that increasing the number of optical phase conjugations in the presence of 10% residual nonlinearity results in a reduction in the performance enhancement owing to an enhancement in the nonlinear noise generation efficiency of the system. We achieve a record 72% optical phase conjugation enabled reach enhancement of the 30x30Gbaud DP-QPSK signals.

Objective: Haptoglobin (Hp) has key immunoregulatory roles that vary with phenotype (Hp1-1, Hp2-1, Hp2-2). Cord blood Hp expression is switched-off in the normal fetus. We hypothesized that in the setting of fetal inflammation placenta becomes inundated with Hp of fetal origin that in turn modulates the output of PGE 2 and MMP-9 in a phenotype dependent manner., Methods: Placentas from 40 pregnancies complicated by preterm birth (PTB) (<37 weeks), without (n = 15) or with (n = 25) intra-amniotic infection and histological chorioamnionitis (HCA) were scored for intensity of Hp immunostaining. Hp mRNA levels were evaluated by PCR. Cord blood Hp levels, switch-on status and phenotypes were determined by ELISA and Western blotting. Using a villous trophoblast explant system we investigated if Hp can modulate the release of PGE 2 and MMP-9 in the presence or absence of lipopolysaccharide (LPS)., Results: All cases with HCA had positive Hp immunoreactivity within fetal vascular spaces. Hp staining intensity correlated with cord blood Hp levels and IL-6. Placentas with and without HCA had similar Hp mRNA levels suggesting Hp immunostaining in the fetal spaces is of fetal rather than placental origin. Both Hp1-1 and Hp2-2 up-regulated PGE 2 release in the presence of LPS (2-fold over the LPS level, P < .05), without affecting MMP-9 concentrations., Conclusions: Fetal Hp switch-on status, a marker of antenatal exposure to intra-amniotic infection/inflammation, can be reliably established through evaluation of archived placental specimens. In the setting of infection/inflammation, Hp enhances placental PGE 2 output thereby supporting the role of the fetus in triggering parturition., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: To improve neonatal outcomes in pregnancies at heightened risk for early-onset neonatal sepsis (EONS), there is a need to identify fetuses that benefit from expectant management as opposed to early delivery. Detectable haptoglobin and haptoglobin-related protein (Hp&HpRP switch-on status) in cord blood has been proposed as a biomarker of antenatal exposure to intra-amniotic infection and/or inflammation (IAI), an important determinant of EONS., Subjects and Methods: We analyzed 185 singleton newborns delivered secondary to preterm premature rupture of membranes (PPROM). In 123 cases, amniocentesis was performed to exclude amniotic fluid (AF) infection. Delivery was indicated for 61 cases with confirmed infection. Women without AF infection (n = 62) and those without amniocentesis (n = 62) were managed expectantly. Interleukin 6 and Hp&HpRP switch-on status were evaluated by ELISA and Western blot. Newborns were followed prospectively for short-term outcomes until hospital discharge or death., Results: Newborns exposed antenatally to IAI had an increased risk of adverse neonatal outcome [OR: 3.0 (95% CI: 1.15-7.59)]. Increasing gestational age [OR: 0.61 (95% CI: 0.52-0.70)] and management with amniocentesis [OR: 0.37 (95% CI: 0.14-0.95)] lowered the newborn's risk of developing adverse outcomes., Discussion: In the setting of PPROM and IAI, early delivery benefits a select subgroup of fetuses that have not yet progressed to Hp&HpRP switch-on status., (© 2016 S. Karger AG, Basel.)

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is often preceded by preterm premature rupture of the membranes (PPROM) without an identifiable cause. Pathological calcification, the deposition of hydroxyapatite (HA) in nonskeletal tissues, has been implicated in degenerative diseases including atherosclerosis and aneurism rupture. Among pathogenic mechanisms, the aberrant aggregation of HA into calciprotein particles (CPPs) and the HA-induced differentiation of mesenchymal cells into osteoblasts (ectopic osteogenesis) have been implicated. We explored the hypothesis that CPPs form in human amniotic fluid (AF), deposit in fetal membranes, and are linked mechanistically to pathogenic pathways favoring PTB. We demonstrated that fetal membranes from women with idiopathic PPROM frequently show evidence of ectopic calcification and expression of osteoblastic differentiation markers. Concentrations of fetuin-A, an endogenous inhibitor of ectopic calcification, were decreased in AF of idiopathic PPROM cases, which reflected their reduced functional capacity to inhibit calcification. Using long-term cultures of sterile AF, we demonstrated coaggregation of HA with endogenous proteins, including fetuin-A. The fetuin-HA aggregates exhibited progressive growth in vitro in a pattern similar to CPPs. When applied to amniochorion explants, AF-derived CPPs induced structural and functional pathological effects recapitulating those noted for PPROM. Our results demonstrate that disruption of protein-mineral homeostasis in AF stimulates the formation and deposition of CPPs, which may represent etiologic agents of idiopathic PPROM. Therapeutic or dietary interventions aimed at maintaining the balance between endogenous HA formation and fetuin reserve in pregnant women may therefore have a role in preventing PTB., (Copyright © 2016, American Association for the Advancement of Science.)

Context: Microbial invasion of the amniotic fluid (AF) cavity stimulates an inflammatory response that involves activin-A, a pleiotropic mediator member of the TGFβ superfamily involved in connective tissue remodeling. The role of AF follistatin, a natural inhibitor of activin-A, in inflammation-induced preterm birth (PTB), has yet to be determined., Objective: The objective of the study was to investigate the relationships between AF activin-A and follistatin in physiological gestation and in pregnancies complicated by PTB and to evaluate a possible role played by the activin-A-follistatin balance in processes leading to PTB and preterm premature rupture of membranes (PPROM)., Study Design: The AF levels of total activin-A and follistatin were immunoassayed in 168 women with a normal pregnancy outcome or PTB with and without intraamniotic inflammation or PPROM. The impact of the activin-A-follistatin imbalance on PTB terminal effector pathways (prostaglandins [prostaglandin E2, prostaglandin F2α] and matrix metalloproteinases [MMP-1, MMP-2, MMP-3, and MMP-9]) was investigated in an amniochorion explant system challenged with lipopolysaccharide (LPS) to mimic inflammation., Results: AF follistatin and the activin-A to follistatin ratio varied with gestational age, both decreasing toward term (P < .001). Activin-A was up-regulated in AF infection (>2-fold elevation in activin-A to follistatin ratio) correlating directly with severity of inflammation (both P < .001). Activin-A increased prostaglandins, MMP-1, and MMP-9 released by amniochorion (P < .05) to LPS-equivalent levels. Follistatin effectively blunted the prostaglandin response to activin-A and LPS and that of MMPs after activin-A but not after LPS challenge., Conclusion: Activin-A and follistatin are part of the complex inflammatory response of the gestational sac to infection and modulate effector pathways leading to PTB. The activin-A to follistatin ratio may play a role in determining the clinical phenotype of PTB as preterm labor or PPROM.

A novel versatile digital signal processing (DSP)-based equalizer using support vector machine regression (SVR) is proposed for 16-quadrature amplitude modulated (16-QAM) coherent optical orthogonal frequency-division multiplexing (CO-OFDM) and experimentally compared to traditional DSP-based deterministic fiber-induced nonlinearity equalizers (NLEs), namely the full-field digital back-propagation (DBP) and the inverse Volterra series transfer function-based NLE (V-NLE). For a 40 Gb/s 16-QAM CO-OFDM at 2000 km, SVR-NLE extends the optimum launched optical power (LOP) by 4 dB compared to V-NLE by means of reduction of fiber nonlinearity. In comparison to full-field DBP at a LOP of 6 dBm, SVR-NLE outperforms by ∼1  dB in Q-factor. In addition, SVR-NLE is the most computational efficient DSP-NLE.

In this paper, we numerically investigate the impact of polarisation mode dispersion on the efficiency of compensation of nonlinear transmission penalties for systems employing one of more inline phase conjugation devices. We will show that reducing the spacing between phase conjugations allows for significantly improved performance in the presence polarisation mode dispersion or a significant relaxation in the acceptable level of polarization mode dispersion. We show that these results are consistent with previously presented full statistical analysis of nonlinear transmission appropriately adjusted for the reduced section length undergoing compensation.

We extend the theory of parametric noise amplification to the case of transmission systems employing multiple optical phase conjugators, demonstrating that the excess noise due to this process may be reduced in direct proportion to the number of phase conjugation devices employed. We further identify that the optimum noise suppression is achieved for an odd number of phase conjugators, and that the noise may be further suppressed by up to 3dB by partial digital back propagation (or fractional spans at the ends of the links).

Objective: To examine the relation between county-level income inequality and rates of child maltreatment., Methods: Data on substantiated reports of child abuse and neglect from 2005 to 2009 were obtained from the National Child Abuse and Neglect Data System. County-level data on income inequality and children in poverty were obtained from the American Community Survey. Data for additional control variables were obtained from the American Community Survey and the Health Resources and Services Administration Area Resource File. The Gini coefficient was used as the measure of income inequality. Generalized additive models were estimated to explore linear and nonlinear relations among income inequality, poverty, and child maltreatment. In all models, state was included as a fixed effect to control for state-level differences in victim rates., Results: Considerable variation in income inequality and child maltreatment rates was found across the 3142 US counties. Income inequality, as well as child poverty rate, was positively and significantly correlated with child maltreatment rates at the county level. Controlling for child poverty, demographic and economic control variables, and state-level variation in maltreatment rates, there was a significant linear effect of inequality on child maltreatment rates (P < .0001). This effect was stronger for counties with moderate to high levels of child poverty., Conclusions: Higher income inequality across US counties was significantly associated with higher county-level rates of child maltreatment. The findings contribute to the growing literature linking greater income inequality to a range of poor health and well-being outcomes in infants and children.

Alzheimer's disease (AD), frontotemporal dementia (FTD) and semantic dementia (SD) are neurodegenerative diseases that differ in their socioemotional presentations. Mutual gaze (i.e. when two individuals make eye contact) is a building block of social behavior that may be differentially affected by these diseases. We studied 13 AD patients, 11 FTD patients, 9 SD patients and 22 normal controls as they engaged in conversations with partners about relationship conflicts. Physiological reactivity was monitored during the conversations and trained raters coded mutual gaze from videotaped recordings. Results indicated that mutual gaze was preserved in AD couples. Mutual gaze was diminished in FTD couples while SD couples showed evidence of greater mutual gaze. SD couples also showed lower physiological reactivity compared to controls. Across patient groups, reduced mutual gaze was associated with greater behavioral disturbance as measured by the Neuropsychiatric Inventory, especially on the disinhibition and apathy subscales. These results point to subtle differences between the three types of dementia in the social realm that help to illuminate the nature of the disease process and could aid in differential diagnosis.

We investigate the design of electronic dispersion compensation (EDC) using full optical-field reconstruction in 10Gbit/s on-off keyed transmission systems limited by optical signal-to-noise ratio (OSNR). By effectively suppressing the impairment due to low-frequency component amplification in phase reconstruction, properly designing the transmission system configuration to combat fiber nonlinearity, and successfully reducing the vulnerability to thermal noise, a 4.8dB OSNR margin can be achieved for 2160km single-mode fiber transmission without any optical dispersion compensation. We also investigate the performance sensitivity of the scheme to various system parameters, and propose a novel method to greatly enhance the tolerance to differential phase misalignment of the asymmetric Mach-Zehnder interferometer. This numerical study provides important design guidelines which will enable full optical-field EDC to become a cost-effective dispersion compensation solution for future transparent optical networks.

The Department of Education, the Association of Schools of Public Health, and national professional societies dedicated to teaching and dissemination of information for health and education in the public sector can form a clearinghouse on information and manpower on Homeland Security by affiliation with Centers for Public Health Preparedness (CPHP). The state licensed or regional societies can contribute further information and guidelines. In the HPS the Science Teacher Workshop (STW) and Public Education (PEC) Committees can assist a CPHP on radiation issues.

The broad based mission statements of public institutions whose charters are to educate the public is analyzed so that common threads pertinent to homeland security action items can be correlated with the public education scope. The intent of the coordination is to ensure that the prevention component in addition to the preparedness issues of homeland security is incorporated into the educational system with short and long term goals.

Ever increasing societal demands for uninterrupted work are causing unparalleled amounts of sleep deprivation among workers. Sleep deprivation has been linked to safety problems ranging from medical misdiagnosis to industrial and vehicular accidents. Microsleeps (very brief intrusions of sleep into wakefulness) are usually cited as the cause of the performance decrements during sleep deprivation. Changes in a more basic physiological phenomenon, attentional shift, were hypothesized to be additional factors in performance declines. The current study examined the effects of 36 hours of sleep deprivation on the electrodermal-orienting response (OR), a measure of attentional shift or capture. Subjects were 71 male undergraduate students, who were divided into sleep deprivation and control (non-sleep deprivation) groups. The expected negative effects of sleep deprivation on performance were noted in increased reaction times and increased variability in the sleep-deprived group on attention-demanding cognitive tasks. OR latency was found to be significantly delayed after sleep deprivation, OR amplitude was significantly decreased, and habituation of the OR was significantly faster during sleep deprivation. These findings indicate impaired attention, the first revealing slowed shift of attention to novel stimuli, the second indicating decreased attentional allocation to stimuli, and the third revealing more rapid loss of attention to repeated stimuli. These phenomena may be factors in the impaired cognitive performance seen during sleep deprivation.

Use of clinical diagnosis as the phenotype for genetic study is discussed, and criteria for appropriate alternative phenotypes are presented. Then, recent research on four alternatives is discussed: (a) resistance to interference from an associative prime, (b) reaction time crossover, (c) creativity, and (d) socioeconomic achievement. It is concluded that resistance to interference from an associative prime and reaction time crossover at 3-sec. preparatory interval level are the most promising of these candidates.

A primary route of inactivation of leukotrienes and their receptor antagonists (LTRA) is metabolism by omega oxidation. SK&F 102922 [5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid] is a LTRA that was designed to be resistant to omega oxidation. Therefore, these experiments were designed to characterize the metabolic fate of [14C]SK&F 102922. Following iv administration of SK&F 102922 (5 mg/kg), 80% of injected radioactivity was excreted in bile in 1 hr. At least five metabolites and parent (18% of administered dose) were present in bile. One metabolite (M1), which accounted for less than 10% of the excreted radioactivity, was monohydroxylated. Three metabolites (M2, M3A, and M3B), which together accounted for greater than 50% of excreted radioactivity, had mass spectra consistent with acyl glucuronides. All three metabolites were alkali labile, whereas only one metabolite (M2) was susceptible to beta-glucuronidase hydrolysis. These data indicate that M3a and M3b are nonglycosidic isomers of M2 that were formed by a nonenzymic reaction involving migration of the aglycone (SK&F 102922) from C-1 to C-2, C-3, or C-4 of glucuronic acid. The 1-O-acyl-beta-glucuronide of SK&F 102922 (M2) exhibits pH dependent rearrangement, with half-lives ranging from 1 to greater than 1000 hr. Therefore, acyl glucuronidation can account for much of the metabolic fate of SK&F 102922 and, potentially, other structurally related LTRAs or endogenous leukotrienes themselves.

This paper will provide an overview of the potential general applicability of chemical hormesis. Evidence will be presented on the occurrence of chemical hormesis by chemical classes studied (e.g. heavy metals, polycylic aromatic hydrocarbons, etc.), by affected biological and toxic end points (e.g. growth enzyme activities, DNA-repair capacity, life span, tumor incidence) and by biological/taxonomic systems. Several specific examples of possible hormetic effects with respect to agents of environmental concern, such as chloroform, will be presented along with a discussion of future research directions.

Both leukotrienes and their receptor antagonists possess substantial pharmacologic activity in in vitro systems, but their duration of action in vivo is extremely short. The exact mechanism of rapid inactivation of these lipids is unknown, but is likely due to metabolism. Therefore, the metabolic fate of a model antagonist 5-(2-dodecylphenyl)-4,6-dithianonanedioic acid (SK&F 102,081) was elucidated in anesthetized guinea pigs. Following iv administration of [14C]SK&F 102,081 (5 mg/kg), 85% of injected radioactivity was excreted in bile in 1 hr. Approximately 6% of the radioactivity in bile was associated with parent. At least 14 metabolites were present in bile, 2 of which accounted for almost 60% of the excreted radioactivity. Identification of biliary metabolites revealed that metabolism occurred by two major routes, omega-oxidation with subsequent beta-oxidation and acyl glucuronidation at approximately a 4:1 ratio. Since current structure-activity relationships suggest that omega-oxidation results in the loss of pharmacologic activity of SK&F 102,081, the rapid loss in pharmacologic activity observed in vivo may be due to rapid metabolism.

The exploratory behaviors of a sample of 11 infants with Down syndrome and 11 nondelayed infants, matched on Bayley mental raw scores and gender, were analyzed. Transitional probabilities and z scores were computed for each possible behavior change as well as frequencies of each behavior. The analyses revealed significant differences in how the 2 samples distribute their exploratory activities. The significant transitional probabilities among the 6 behavioral states revealed a pattern of similarities and differences. In general, both groups of infants organized their exploratory activities in a similar manner. However, there were differences that appeared to depend on the level of exploratory sophistication. The results are discussed in the context of the similarities and differences between the samples.