Search

Background: Many health care organizations offer pediatric infusions in outpatient infusion centers or, as in our organization, in a hospital-based outpatient Pediatric Infusion Therapy Center (PITC). When restrictions related to the COVID-19 pandemic decreased our PITC appointment capacity by 40%, other patient and family satisfaction issues were exacerbated. We implemented a new approach to pediatric infusions with the aim of improving patient and family satisfaction and reducing the amount of time in an appointment itinerary without negatively affecting patient safety. Methods: Our team used a phased approach to pilot the administration of short chemotherapy infusions in the same outpatient clinic examination rooms where consultation and routine office visits were conducted. Patients saw their specialist for an examination and, if clinically indicated, their infusion was administered in the same room. Appointment itineraries were then completed. The team tracked efficiency, satisfaction, and safety metrics related to the new process. Results: All efficiency metrics improved. No harm came to the 49 unique patients who received a total of 184 infusions. Patient appointment itineraries were shortened by an average of 1.03 hr. Satisfaction survey responses indicated a clear preference (93%) for the new process. Discussion: The novel approach of offering short infusions in outpatient clinic examination rooms provides an opportunity to ease capacity constraints and further increase patient and family satisfaction. This method may be especially helpful for health care organizations when external influences (e.g., lack of physical space, challenging patient volumes, and pandemics) necessitate a change.

IntroductionNeuroinflammation and metabolic dysfunction are early alterations in Alzheimer’s disease brain that are thought to contribute to disease onset and progression. Glial activation due to protein deposition results in cytokine secretion and shifts in brain metabolism, which have been observed in Alzheimer’s disease patients. However, the mechanism by which this immunometabolic feedback loop can injure neurons and cause neurodegeneration remains unclear.MethodsWe used Luminex XMAP technology to quantify hippocampal cytokine concentrations in the 5xFAD mouse model of Alzheimer’s disease at milestone timepoints in disease development. We used partial least squares regression to build cytokine signatures predictive of disease progression, as compared to healthy aging in wild-type littermates. We applied the disease-defining cytokine signature to wild-type primary neuron cultures and measured downstream changes in gene expression using the NanoString nCounter system and mitochondrial function using the Seahorse Extracellular Flux live-cell analyzer.ResultsWe identified a pattern of up-regulated IFNγ, IP-10, and IL-9 as predictive of advanced disease. When healthy neurons were exposed to these cytokines in proportions found in diseased brain, gene expression of mitochondrial electron transport chain complexes, including ATP synthase, was suppressed. In live cells, basal and maximal mitochondrial respiration were impaired following cytokine stimulation.ConclusionsAn Alzheimer’s disease-specific pattern of cytokine secretion reduces expression of mitochondrial electron transport complexes and impairs mitochondrial respiration in healthy neurons. We establish a mechanistic link between disease-specific immune cues and impaired neuronal metabolism, potentially causing neuronal vulnerability and susceptibility to degeneration in Alzheimer’s disease.

The aggregation of the amyloid beta (Aβ) peptide is associated with Alzheimer’s disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of the neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that GM1 not only promotes the formation of Aβ fibrils but also facilitates the maintenance of Aβ42 oligomers on liposome membranes. We structurally characterize the Aβ42 oligomers formed on the membrane and find that GM1 captures Aβ by binding to its arginine-5 residue. To interrogate the mechanism of Aβ42 oligomer toxicity, we design a new liposome-based Ca(2+)-encapsulation assay and provide new evidence for the Aβ42 ion channel hypothesis. Finally, we determine the toxicity of Aβ42 oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early Aβ oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.

The present study examined how adults living in the United States perceive children’s developmentally-appropriate and problematic sexual behaviors before and after receiving psychoeducation on thes...

The ε4 variant of apolipoprotein E (APOE) is the strongest and most common genetic risk factor for Alzheimer’s disease (AD). While the mechanism of conveyed risk is incompletely understood, promotion of inflammation, dysregulated metabolism, and protein misfolding and aggregation are contributors to accelerating disease. Here we determined the concurrent effects of systemic metabolic changes and brain inflammation in young (3-month-old) and aged (18-month-old) male and female mice carrying theAPOE4gene. Using functional metabolic assays alongside multivariate modeling of hippocampal cytokine levels, we found that brain cytokine signatures are predictive of systemic metabolic outcomes, independent of AD proteinopathies. Male and female mice each produce different cytokine signatures as they age and as their systemic metabolic phenotype declines, and these signatures areAPOEgenotype dependent. Ours is the first study to identify a quantitative and predictive link between systemic metabolism and specific pathological cytokine signatures in the brain. Our results highlight the effects of APOE4 beyond the brain and suggest the potential for bi-directional influence of risk factors in the brain and periphery.Abstract Figure

BACKGROUND Mentally ill children with intellectual disabilities do not always receive the services they need for effective change at psychiatric hospitals, as their verbal limitations render standard procedures in diagnostics and therapy difficult or impossible, as their ability to transfer insights acquired in one setting to another is impaired and as their families and caretakers are often overwhelmed by their needs. This is why an integral vision for children with intellectual disabilities is presented. Drawing on three case reports, it is highlighted how an interdisciplinary approach, a changed hospital set-up and constant interplay between therapy and pedagogy, between services to the child and to its caregivers can help overcome these difficulties. METHOD Case reports. CONCLUSIONS Some children risk being mistakenly treated as intellectually disabled. If testing reveals, for example, autism with a mild learning disability, psychoeducation and the pedagogical training for (special school) personnel can help prevent underachievement and bring about a setting that can help the child flourish. Both sensitive care and pedagogical intervention that fit the developmental age of severely intellectually disabled children can prevent their receiving sedatives to treat aggressive behaviour. Substantial and lasting shifts in mood, even happiness can result if parents and caregivers get the pedagogical training and the assistance they need to take care of their children. Reliable and well-structured pedagogical training and environments can enhance and often substitute for unavailable therapeutic interventions for this specific group. With some profound intellectually and multiply disabled children, beginning medical treatment at home may not be safe. The (in)effectiveness of specific psychiatric medications needs to be monitored by observations however. For reliable results with intellectually disabled children, a clinical setting that resembles their everyday life is needed.

Prior literature illustrates that sexual minority people (e.g., bisexual, gay, queer) are at increased vulnerability for sexual violence victimization compared to heterosexual peers, including while in college. However, the study of sexual violence perpetration in sexual minority populations, much less specifically sexual minority college men, has been neglected. This article reviews the literature and presents a secondary data analysis of a systematic review on college men’s sexual perpetration rates and associated methodology. We also conducted analyses to summarize available literature regarding publishing dates, authors, and data inclusivity. Methods: We downloaded the dataset and associated materials from Mendeley.com’s data archive. Results: To our surprise, we could not analyze sexual perpetration prevalence rates in sexual minority men using the systematic review data due to absence of reported data across all 77 independent samples including over 5,500 male participants. We found no significant relationship between inclusion of sexual minority men and the use of measurement strategies specialized to assess sexual minority needs. We did find a positive relationship between recency of publication and the inclusion of sexual minority men, r(76) = .24, p = .03, and that most authors/co-authors were women (72%). Conclusions: Preventing perpetration is central to ending sexual violence; therefore, future research should include sexual minority people and use appropriate methodology in the investigation of sexual perpetration characteristics and patterns.

Glioblastoma (GBM) remains one of the most difficult to treat malignancies facing modern medicine. The strong migratory and invasive capacity of GBM cells allows for diffuse invasion into neighboring healthy brain which presents a significant hurdle for complete surgical resection of these tumors. Unsurprisingly, even after receiving maximal surgical resection, radiation and chemotherapy, the majority of GBM patients end up with recurrent disease. Increased expression levels of the homeostatic iron regulator gene (HFE) in brain tumors such as GBM have been associated with poorer outcomes. In order to better understand how HFE expression impacts the adhesive and migratory capacity of GBM, we utilized syngeneic mouse glioma models (KR158, CT2A) that have been transfected to either over-express or under-express HFE. We observed that knocking down HFE in the KR158 model resulted in significantly decreased migratory capacity as well as decreased adhesion to fibronectin and artificial basement membrane. Likewise, overexpressing HFE in a CT2A model resulted in increased adhesion to fibronectin or artificial basement membrane. Since HFE is known to regulate iron uptake, we studied how modulating the iron status of GBM cells impacted their ability to migrate and adhere. We found that increasing the iron pool of these mouse glioma models by exposure to exogenous iron compounds decreased migratory capacity. To better understand mechanistically how HFE and iron status impacted migration and adhesion, we probed how expression of integrins and their downstream signaling molecules, the Rho GTPases were altered in response to iron. We found that exposure to iron decreased levels of the Rho GTPases Cdc42 and RhoA. Furthermore, cells that overexpressed HFE were found to have increased expression of integrin β1 and integrin α5 suggesting that HFE and iron may impact integrins and their downstream signaling pathways to alter migration of GBM cells.

Background While the unique marine and coastal environment of the Baltic Sea provides numerous ecosystem services, its ecosystems are under pressure due to the intensification and diversification of anthropogenic uses. This present work constitutes a systematic map of the evidence of the impacts of ecosystem services and disservices on human health and well-being. The aim is to create a better understanding of the threats of unsustainable management or the benefits of sustainable management of the Baltic Sea and the impacts these may have on the health and well-being of human populations and present these findings to policy advisors. The mapping process is described, and the characteristics of the evidence base are presented. Methods The applied method has been previously published in a systematic map protocol. Literature searches were carried out in English considering published peer-reviewed literature from traditional scientific journals and scientific reports from the grey literature, using synthesis software. A total of 17 databases were searched. Articles were screened in stages at title and abstract stage, then full-text stage. Geographic limitations were placed on the searches in accordance with research funders call, however, watersheds that had an impact on the Baltic Sea marine and coastal regions were considered. We used the more open PEO format, where population (P) included the human populations within the marine and coastal environment of the Baltic Sea region, exposure (E) related to the Baltic Sea ecosystems services and disservices, and the outcome (O) included all aspects of human health and well-being. After full-text screening articles selected for inclusion were searched for metadata connected to bibliographic information, ecosystem services, health and well-being outcomes and policy relevance. Review findings Out of 6456 hits only 460 studies discussed either health or well-being indicators to some extent. Of these, only 67 explicitly mentioned ecosystem services and health and well-being indicators. However, few in this subset engaged with the topic of ecosystem services or disservices and health and well-being in depth. Studies are increasingly relating the two concepts but currently it is mainly studies focussed on cultural ecosystem services that deal with the concept of health and well-being to a greater degree. Studies in the medical literature relating to impacts on health from exposure to the Baltic Sea did not relate their findings to ecosystem services. The database of 67 studies is attached as Additional file 5. Conclusions Ecosystem services play an important role in human health and well-being; however, we found few studies that explicitly examine these impacts in detail. Further research is needed to link the health and well-being outcomes from the Baltic Sea to the ecosystem services supplied and therefore to demonstrate the benefits and disservices provided by the Baltic Sea ecosystems to human populations.

The nature of the 1 − and 2 − excited states in Be 10 is studied using the Be 11 ( p , d ) transfer reaction in inverse kinematics at 10A MeV at TRIUMF ISAC-II, in particular to assess whether either of them can be considered as an excited halo state. The angular distributions for both states are extracted using deuteron- γ coincidences and analyzed using a transfer model taking into account one-step and two-step processes. A good fit of the angular distributions is obtained considering only the one-step process, whereby an inner p 3 / 2 neutron of Be 11 is removed, leaving the halo neutron intact. Higher-order processes however cannot be rejected. The small spectroscopic factors extracted suggest that the structure of both states is not uniquely halo-like, but rather display a more complex configuration mixing cluster and halo structures. Further insights are limited, as this experiment specifically probed the halo-like (but not cluster-like) Be 11 ( 1 / 2 + ) ⊗ ( ν p 3 / 2 ) − 1 configuration in both states.

The aggregation of amyloid beta (Aβ) peptide is associated with Alzheimer’s disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that GM1 not only promotes the formation of Aβ fibrils, but also facilitates the maintenance of Aβ oligomers on liposome membranes. We structurally characterize the Aβ oligomers formed on the membrane and find that GM1 captures Aβ by binding to its arginine-5 residue. To interrogate the mechanism of Aβ oligomer toxicity, we design a new liposome-based Ca2+-encapsulation assay and provide new evidence for the Aβ ion channel hypothesis. Finally, we conduct cell viability assay to determine the toxicity of Aβ oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early Aβ oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.

Background: Prescription rates for major classes of psychotropic medication were examined among respondents with and without histories of trauma and PTSD. While traumatized patients access primary health care at higher rates than normative counterparts, the extent to which they rely on psychiatric medications has not been well established. Methods: This study surveyed college (N=2,320) and national (N=663) respondents. Trauma history was defined using the primary DSM-5 diagnostic criterion for Post- Traumatic Stress Disorder. Four hypotheses were tested: 1) medication reliance was expected to occur more frequently among respondents reporting a trauma history and PTSD than normative counterparts; 2) medication reliance was expected to occur more frequently among respondents reporting a trauma history without PTSD than normative (no trauma) counterparts; 3) gender differences in these associations between trauma exposure and medication history were not expected; 4) associations between trauma exposure and medication history were expected to be similar for college and national respondents. Results: Support was found for these four hypotheses. Significant associations between self-reported trauma and reliance on psychotropic medications remained even after control of variance associated with gender, sample composition, and PTSD diagnosis. Recollections of a traumatic event as defined by the DSM-V criteria for PTSD increased the odds of being prescribed five different classes of psychiatric medication. Conclusion: Trauma exposure both with and without co-occurring mental health conditions was associated with higher reliance on psychotrophic medications. The clinical implications of these patterns remain unclearly delineated. The cross-sectional correlation analyses relied upon in this study precluded meaningful onferences regarding the causality and/or directionality of these relationships.

Background Patients suffering from schizophrenia spectrum disorders demonstrate various cognitive deficiencies, the most pertinent one being impairment in autobiographical memory. This paper reviews quantitative research investigating deficits in the content, and characteristics, of autobiographical memories in individuals with schizophrenia. It also examines if the method used to activate autobiographical memories influenced the results and which theoretical accounts were proposed to explain the defective recall of autobiographical memories in patients with schizophrenia. Methods PsycINFO, Web of Science, and PubMed databases were searched for articles published between January 1998 and December 2018. Fifty-seven studies met the inclusion criteria. All studies implemented the generative retrieval strategy by inducing memories through cue words or pictures, the life-stage method, or open-ended retrieval method. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement guidelines were followed for this review. Results Most studies reported that patients with schizophrenia retrieve less specific autobiographical memories when compared to a healthy control group, while only three studies indicated that both groups performed similarly on memory specificity. Patients with schizophrenia also exhibited earlier reminiscence bumps than those for healthy controls. The relationship between comorbid depression and autobiographical memory specificity appeared to be independent because patients’ memory specificity improved through intervention, but their level of depression remained unchanged. The U-shaped retrieval pattern for memory specificity was not consistent. Both the connection between the history of attempted suicide and autobiographical memory specificity, and the relationship between psychotic symptoms and autobiographical memory specificity, remain inconclusive. Patients’ memory specificity and coherence improved through cognitive training. Conclusions The overgeneral recall of autobiographical memory by patients with schizophrenia could be attributed to working memory, the disturbing concept of self, and the cuing method implemented. The earlier reminiscence bump for patients with schizophrenia may be explained by the premature closure of the identity formation process due to the emergence of psychotic symptoms during early adulthood. Protocol developed for this review was registered in PROSPERO (registration no: CRD42017062643).

BACKGROUND Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P

Gamma-Ray Infrastructure For Fundamental Investigations of Nuclei, GRIFFIN, is a new high-efficiency γ -ray spectrometer designed for use in decay spectroscopy experiments with low-energy radioactive ion beams provided by TRIUMF’s Isotope Separator and Accelerator (ISAC-I) facility. GRIFFIN is composed of sixteen Compton-suppressed large-volume clover-type high-purity germanium (HPGe) γ -ray detectors combined with a suite of ancillary detection systems and coupled to a custom digital data acquisition system. The infrastructure and detectors of the spectrometer as well as the performance characteristics and the analysis techniques applied to the experimental data are described.

Research examining trauma, memory, and mental health among refugee and asylum-seeking people has increased in recent years. We systematically reviewed empirical work focusing on the link between autobiographical memory and mental health among these populations. The review protocol was registered with PROSPERO (CRD42018095888). Six major databases were searched in August-2020 with no time limit for publication. Following PRISMA Statement guidelines, 22 articles reporting ten quantitative, nine qualitative, and three mixed-method studies were selected from 254 articles identified in the initial search. A basic convergent and qualitative meta-integration technique was employed for data extraction. Four recurrent themes were extracted: (1) memory activation method, (2) memory features, (3) memory content, and (4) refugee mental health. Theme 1 illustrates that narrative interviews, important event recall, and cue word methods were used in most studies. Theme 2 highlights that memories of refugee people were often less specific, inconsistent, and negative-focused. Retrieval failure was also common among these people. Theme 3 reveals that refugee and asylum-seeking people frequently discussed their abandoned identities, lost resources, injustices, ongoing sufferings, and pointless futures. Finally, theme 4 identifies the prevalence of various mental health conditions like Post-traumatic Stress Disorder, depression, helplessness, and anger among these people. The results are discussed in the context of the current autobiographical memory and mental health theories, considering refugee-specific experiences in the asylum process and refugee status.

To evaluate the correlation between an uncapped, actual body weight-based unfractionated heparin dosing strategy, we performed a body mass index-based subanalysis of a previously reported pediatric cohort. Nearly half (45%) of obese patients were supra-therapeutic on initial anti-FXa assessment. Obese patients achieved therapeutic anti-FXa significantly faster than nonobese patients (median 4 vs 12 hours, P = .0192) and were more likely to have any supra-therapeutic anti-FXa levels (77% vs 35%; P = .0021). There was no statistically significant difference in major or clinically relevant nonmajor bleeding rates between weight categories (P = .69). Prospective pediatric studies are warranted to confirm our findings.

The ecosystem service (ES) approach usually addresses soil erosion as the regulating service control of erosion rates or soil retention. In addition to the assessment of this regulating ES, mitigated impacts on soil-related ES by preventing soil erosion can be assessed. This study presents a scenario-based approach for the assessment of the impact of soil erosion on soil-related ES. The assessment approach was tested in agricultural landscapes in Northern Germany, combining mapping and assessment of soil-related ES. In six scenarios, the degradation of soils due to soil erosion was simulated by the calculation of soil profile reductions. The scenarios represent two levels of impact with three time steps (+50, +100, +150 years). In the scenarios for the structural impact, the potential soil erosion rates were extrapolated into the future to generate spatially explicit information on degraded soils. In the scenarios for the mitigated impact, the actual soil erosion rates were extrapolated. Four soil-related ES were assessed for the initial state and the scenarios crop provision, water filtration, water flow regulation and fresh water provision. The comparison of the potential service supply of the four soil-related ES in the scenarios enabled the assessment of the long-term effect of the ES control of erosion rates. The mitigated reduction in the potential service supply for three of the considered ES (crop provision, water filtration, water flow regulation) is large and highlights the importance of sustainable soil management. Contrary to this, the ES fresh water provision benefits of erosion-induced soil profile reductions.

The $\beta^-$ decay of $^{47}$K to $^{47}$Ca is an appropriate mechanism for benchmarking interactions spanning the $sd$ and $pf$ shells, but current knowledge of the $\beta^-$-decay scheme is limited. We have performed a high-resolution, high-efficiency study of the $\beta^-$-decay of $^{47}$K with the GRIFFIN spectrometer at TRIUMF-ISAC. The study revealed 48 new transitions, a more precise value for the $^{47}$K half-life (17.38(3)~s), and new spin and parity assignments for eight excited states. Levels placed for the first time here raise the highest state observed in $\beta^-$ decay to within 568(3) keV of the $Q$-value and confirm the previously measured large $\beta^-$-decay branching ratios to the low-lying states. Previously unobserved $\beta^-$-feeding to 3/2$^+$ states between 4.5 and 6.1~MeV excitation energy was identified with a total $\beta^-$-feeding intensity of 1.29(2)\%. The sum of the $B(GT)$ values for these states indicates that the $1s_{1/2}$ proton hole strength near this excitation energy is comparable to the previously known $1s_{1/2}$ proton and neutron hole strengths near 2.6 MeV.

INTRODUCTION Enoxaparin is commonly used to treat pediatric thrombosis. Several small retrospective studies have suggested that infants and young children require higher enoxaparin doses to achieve therapeutic anti-factor Xa levels compared with adults. MATERIALS AND METHODS This is a retrospective study of hospitalized children who received enoxaparin for the treatment of thrombosis at a free-standing children's hospital. The primary objective was to ascertain the enoxaparin dose required to achieve an anti-factor Xa level of 0.5 to 1.0 U/mL among 4 age groups in a large cohort of infants and young children between 60 days and 5 years of age. RESULTS A total of 176 infants and children were evaluated. The majority of patients were less than 1 year of age (n=104). An inverse relationship between enoxaparin dose needed to achieve therapeutic anti-factor Xa levels and patient age was noted, particularly in the first year of life. Patients who were 60 days to less than 7 months at the time of enoxaparin initiation (n=73) required the highest mean dose among the age groups at 1.73 mg/kg subcutaneously every 12 hours (P

12 pags., 16 figs., 2 tabs., Background: Neutron-rich nuclei around neutron number N=60 show a dramatic shape transition from spherical ground states to prolate deformation in Sr98 and heavier nuclei. Purpose: The purpose of this study is to investigate the single-particle structure approaching the shape transitional region. Method: The level structures of neutron-rich Sr93,94,95 were studied via the H2(Sr94,95,96,t) one-neutron stripping reactions at TRIUMF using a beam energy of 5.5 AMeV. γ-rays emitted from excited states and recoiling charged particles were detected by using the TIGRESS and SHARC arrays, respectively. States were identified by gating on the excitation energy and, if possible, the coincident γ radiation.Results: Triton angular distributions for the reactions populating states in ejectile nuclei Sr93,94,95 were compared with distorted wave Born approximation calculations to assign and revise spin and parity quantum numbers and extract spectroscopic factors. The results were compared with shell-model calculations and the reverse (d,p) reactions and good agreement was obtained. Conclusions: The results for the H2(Sr94,t)Sr93 and H2(Sr95,t)Sr94 reactions are in good agreement with shell-model calculations. A two-level mixing analysis for the 0+ states in Sr94 suggest strong mixing of two shapes. For the H2(Sr96,t)Sr95 reaction the agreement with the shell-model is less good. The configuration of the ground state of Sr96 is already more complex than predicted, and therefore indications for the shape transition can already be observed before N=60., We acknowledge support from the Science and Technologies Facility Council (UK, Grants No. EP/D060575/1 and No. ST/L005727/1), the National Science Foundation (US, Grant No. PHY-1306297), the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation and the British Columbia Knowledge and Development Fund. TRIUMF receives federal funding via a contribution through the National Research Council Canada. K.W. acknowledges the support from the Spanish Ministerio de Economía, Industria y Competitividad, Gobierno de España RYC-2017-22007.

Sequence time-domain reflectometry (STDR) and spread spectrum time-domain reflectometry (SSTDR) detect, locate, and diagnose faults in live (energized) electrical systems. In this paper, we survey the present SSTDR literature for discussions on theory, algorithms used in its analysis, and its more prominent implementations and applications. Our review includes both scientific litera-ture and selected patents. We also discuss future applications of SSTDR.

The cross-linked pentapeptides (2R, 7R)-diaminooctanedioyl- bis(Tyr-Arg-Leu-Arg-Tyr-amide) ((2R, 7R)BVD- 74D, (2R, 7R)-1) and octanedioyl-bis(Tyr-Arg-Leu-ArgTyr- amide) (2) as well as the pentapeptide Ac-Tyr-Arg-LeuArg- Tyr-amide (3) were previously described as neuropeptide Y Y-4 receptor (Y4R) partial agonists. Here, we report on a series of analogues of (2R, 7R)-1 and 2 in which Arg(2), Leu(3), or Arg(4) were replaced by the respective aza-amino acids. The replacement of Arg(2) in 3 with a carbamoylated arginine building block and the extension of the N-terminus by an additional arginine led to the high-affinity hexapeptide Ac-Arg-Tyr-N-omega-[(4-aminobutyl) aminocarbonyl] Arg-Leu-Arg-Tyr-amide (35), which was used as a precursor for a D-amino acid scan. The target compounds were investigated for Y4R functional activity in assays with complementary readouts: aequorin Ca2+ and beta-arrestin 1 or beta-arrestin 2 assays. In contrast to the parent compounds, which are Y4R agonists, several ligands were able to suppress the effect elicited by the endogenous ligand pancreatic polypeptide and therefore represent a novel class of peptide Y4R antagonists.

The neuropeptide Y (NPY) Y4 receptor (Y4R) is involved in energy homeostasis and considered a potential drug target for the treatment of obesity. Only a few molecular tools, i.e., radiolabeled and fluorescent ligands, for the investigation of the Y4R were reported. Previously, [Lys4]hPP proved to be an appropriate full-length PP analog to prepare a fluorescent ligand by derivatization at the e-amino group. To preclude oxidation upon long-term storage, we replaced the two methionine residues in [Lys4]hPP by norleucine and prepared the corresponding [3H]propionylated ([3H]12) and cyanine labeled (13) peptides, which were characterized and compared with a set of reference compounds in binding (Y1, Y2, Y4, and Y5 receptors) and functional (luciferase gene reporter, beta-arrestin-1,2) Y4R assays. Both molecular probes proved to be useful in radiochemical and flow cytometric saturation and competition Y4R binding experiments. Most strikingly, there was a different influence of the composition of buffer on equil...

We report on high-statistics data from the $\beta^-$ decay of the $^{46}$K $J^{\pi}$ = 2$^-$ ground state taken with the GRIFFIN spectrometer located at the TRIUMF-ISAC facility. In total, 199 $\gamma$ rays and 42 excited states were placed in the level scheme, and from the observed $\beta$ feeding and angular correlations of pairs of cascading $\gamma$ rays, it was possible to assign spins and parities to excited states and determine mixing ratios for selected $\gamma$ rays. The level structure of $^{46}$Ca is compared to theoretical predictions from a microscopic valence-space Hamiltonian derived from two- (NN) and three-nucleon (3N) forces. These calculations are in reasonable agreement with the experimental data and indicate that the protons in this region are not as inert as would be expected for semi-magic nuclei.

Background: The region around neutron number N=60 in the neutron-rich Sr and Zr nuclei is one of the most dramatic examples of a ground-state shape transition from (near) spherical below N=60 to strongly deformed shapes in the heavier isotopes. Purpose: The single-particle structure of Sr95-97 approaching the ground-state shape transition at Sr98 has been investigated via single-neutron transfer reactions using the (d,p) reaction in inverse kinematics. These reactions selectively populate states with a large overlap of the projectile ground state coupled to a neutron in a single-particle orbital. Method: Radioactive Sr94,95,96 nuclei with energies of 5.5 AMeV were used to bombard a CD2, where D denotes H2, target. Recoiling light charged particles and γ rays were detected using a quasi-4π silicon strip detector array and a 12-element Ge array. The excitation energy of states populated was reconstructed employing the missing mass method combined with γ-ray tagging and differential cross sections for final states were extracted. Results: A reaction model analysis of the angular distributions allowed for firm spin assignments to be made for the low-lying 352, 556, and 681 keV excited states in Sr95 and a constraint has been placed on the spin of the higher-lying 1666 keV state. Angular distributions have been extracted for ten states populated in the H2(Sr95,p)Sr96 reaction, and constraints have been provided for the spins and parities of several final states. Additionally, the 0, 167, and 522 keV states in Sr97 were populated through the H2(Sr96,p) reaction. Spectroscopic factors for all three reactions were extracted. Conclusions: Results are compared to shell-model calculations in several model spaces and the structure of low-lying states in Sr94 and Sr95 is well described. The spectroscopic strength of the 0+ and 2+ states in Sr96 is significantly more fragmented than predicted. The spectroscopic factors for the H2(Sr96,p)Sr97 reaction suggest that the two lowest-lying excited states have significant overlap with the weakly deformed ground state of Sr96, but the ground state of Sr97 has a different structure.

Heat stroke is a life-threatening condition characterized by loss of thermoregulation and severe elevation of core body temperature, which can cause organ failure and damage to the central nervous system. While no definitive test exists to measure heat stroke severity, immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. In this study, we used a mouse model of classic heat stroke to test the effect of immune challenge on pathology. Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases presenting with the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals, and these increases correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. We conclude that heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection, and that coagulation markers may serve as an accessible biomarker for heat stroke severity and therapeutic strategies.Key pointsA signature of pro-coagulation markers predicts circadian core body temperature and levels of organ damage in heat strokeChanges in coagulopathy-related gene expression are evidenced before histopathological organ damage

In 2016, 43000 members of 159 wine cooperatives were growing wine on about 30% of the total German viticultural area. Those members have different origin, belong to different age groups, their business dispose over different sizes and business models, and all members have individual desires and interests. Thus, the task of the cooperative management and boards is to align the resulting heterogeneous individual aims and interests with the overall aims and interests of the cooperative. Hence the aim of the paper is to answer the question: How the heterogenous member interests can be aligned within the cooperative? In order to answer this question four in-depth expert interviews have been conducted.