Hypercapnic ventilatory response in mice lacking the 65 kDa isoform of Glutamic Acid Decarboxylase (GAD65)

BACKGROUND: Recent reports have shown that there are developmental changes in the ventilatory response to hypercapnia in the rat. These are characterized by an initial large response to carbon dioxide immediately after birth followed by a decline with a trough at one week of age, followed by a return in sensitivity. A second abnormality is seen at postnatal day 5 (P5) rats in that they cannot maintain the increase in frequency for 5 min of hypercapnia. In mice lacking GAD65 the release of GABA during sustained synaptic activation is reduced. We hypothesized that this developmental pattern would be present in the mouse which is also less mature at birth and that GABA mediates this relative respiratory depression. METHODS: In awake C57BL/6J and GAD65-/- mice the ventilatory response to 5% carbon dioxide (CO2) was examined at P2, P4, P6, P7, P12.5, P14.5 and P21.5, using body plethysmography. RESULTS: Minute ventilation (VE) relative to baseline during hypercapnia from P2 through P7 was generally less than from P12.5 onwards, but there was no trough as in the rat. Breaking VE down into its two components showed that tidal volume remained elevated for the 5 min of exposure to 5% CO2. At P6, but not at other ages, respiratory frequency declined with time and at 5 min was less that at 2 and 3 min. GAD65-/- animals at P6 showed a sustained increase in respiratory rate for the five mins exposure to CO2. CONCLUSION: These results show, that in contrast to the rat, mice do not show a decline in minute ventilatory response to CO2 at one week of age. Similiar to the rat at P5, mice at P6 are unable to sustain an increase in CO2 induced respiratory frequency and GAD65 contributes to this fall off

Substantial Dose-response Relationship with Clinical Outcome for Lung Stereotactic Body Radiotherapy (SBRT) Delivered via Online Image Guidance

Purpose: To examine potential tumor dose-response relationships with various non-small cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Cumulative childhood trauma and complex psychiatric symptoms in pregnant women and expecting men

Background: Women and men having been exposed to childhood trauma would be at high risk of various mental health symptoms while awaiting a child. This study aimed to evaluate the association between cumulative childhood trauma and the accumulation of symptoms belonging to different psychiatric problems in pregnant women and expecting men. Methods: We first examined prevalence rates of childhood trauma across our samples of 2853 pregnant women and 561 expecting men from the community. Second, we evaluated the association between cumulative childhood trauma and symptom complexity (i.e., the simultaneous presentation of symptoms belonging to multiple psychiatric problems) using subsamples of 1779 pregnant women and 118 expecting men. Participants completed self-reported measures of trauma (Childhood Trauma Questionnaire) and psychiatric symptoms (PTSD Checklist for DSM-5; Kessler Psychological Distress Scale; State-Trait Anger Expression Inventory-2; Self and Interpersonal Functioning Scale). Results: Trauma was more frequent in pregnant women than in expecting men and in participants reporting sociodemographic risk factors than in those not reporting any. A dose-response relationship was observed between the number of different traumas reported by pregnant women and expecting men and the complexity of their psychiatric symptoms, even when controlling for the variance explained by other risk factors. Women having been exposed to cumulative childhood trauma were 4.95 times more at risk of presenting comorbid psychiatric problems during pregnancy than non-exposed women. Conclusions: Childhood trauma is frequent in the general population of pregnant women and expecting men and is associated with symptom complexity during the antenatal period. These findings call for delivering and evaluating innovative trauma-informed antenatal programs to support mental health and adaptation to parenthood in adults having been exposed to childhood trauma. © 2021, The Author(s)

Beyond abuse and neglect: Validation of the childhood interpersonal trauma inventory in a community sample of adults

Abstract Introduction Childhood trauma is not restricted to abuse or neglect and other potentially traumatic experiences need to be pondered in practice and research. The study aimed to collect validity evidence of a new measure of exposure to a broad range of potentially traumatic experiences, the Childhood Interpersonal Trauma Inventory (CITI), by evaluating whether the CITI provides important additional information compared to a gold standard measure of childhood trauma. Methods The sample consisted of 2,518 adults who completed the CITI and self-reported measures of trauma (Childhood Trauma Questionnaire; CTQ) and psychiatric symptoms (PTSD Checklist for DSM-5; Kessler Psychological Distress Scale; Dissociative Experiences Scale). Results First, the sensitivity to properly detect participants having been exposed to childhood maltreatment, as measured by the CTQ (here used as the gold standard), ranged between 64.81% and 88.71%, and the specificity ranged between 68.55% and 89.54%. Second, hierarchical regressions showed that the CITI predicted between 5.6 and 14.0% of the variance in psychiatric symptoms while the CTQ only captured a very small additional part of variance (0.3 to 0.7%). Finally, 25% (n = 407) of CTQ-negative participants screened positive at the CITI. The latter reported higher severity of psychiatric symptoms than participants without trauma, suggesting that the CITI permits the identification of adults exposed to significant traumas that remain undetected using other well-validated measures. Discussion The findings underscore the utility of the CITI for research purposes and the latter’s equivalence to a gold standard self-reported questionnaire to predict negative outcomes

Paucity of intervention research in childhood maltreatment contrasts with the long known relation with mental health disorders: is trauma research translational enough?

The damaging consequences of child abuse and neglect for child development and psychiatric disorders have been known for decades. However, there would be a relative paucity of translational research on childhood maltreatment in comparison to the numerous correlational studies in the field. To assess the extent to which previous research on childhood maltreatment addressed intervention, we reviewed all articles on child abuse and neglect published in 2016 and evaluated the main objective of each study. References were identified through PsycINFO (ƙ = 2139) and Medline (ƙ = 2955). Of the 3792 studies retained after removal of overlapping references, 1157 met inclusion criteria. The main objective of each study was coded according to one of the following categories: Consequences, Mechanisms, Intervention, Prevention and Others. The review showed that half of the studies (ƙ = 572; 50%) described the damaging consequences of child abuse and neglect. A mere 19% of the studies (ƙ = 225) aimed to identify mediators or moderators of the association between childhood maltreatment and outcome. Only 6% (ƙ = 66) of studies reported on treatments and 2% (ƙ = 29) on preventive interventions. The remaining articles (23%, ƙ = 265) focused on other topics, such as the assessment of childhood trauma (ƙ = 33), epidemiology (ƙ = 118) and legal or organizational issues (ƙ = 114). Our results revealed an unquestionable paucity of research published on interventions and a relatively scarce number of mechanistic studies that nonetheless may provide meaningful practical orientations for clinical practice and future research

The Impact of Slice Interval and Equation on the Accuracy of Magnetic Resonance Image Estimation of Quadriceps Muscle Volume in End Stage Liver Disease

INTRODUCTION: End stage liver disease (ESLD) is associated with loss of muscle mass and function, known as sarcopenia, which can increase the risk of complications of ESLD, hospitalization and mortality. Therefore, the accurate assessment of muscle mass is essential to evaluate sarcopenia in ESLD. However, manual segmentation of muscle volume (MV) can be laborious on cross-sectional imaging, due to the number of slices that require analysis. This study aimed to investigate the impact of reducing the number of slices required for MV estimation. Further, we aimed to compare two equations utilized in estimating MV (cylindrical and truncated cone). METHODS: Thirty eight ESLD patients (23 males; 54.8 ± 10.7 years) were recruited from the Queen Elizabeth University Hospital Birmingham. A 3T MRI scan was completed of the lower limbs. Quadriceps MV was estimated utilizing 1-, 2-, 3-, and 4 cm slice intervals with both cylindrical and truncated cone equations. Absolute and relative error (compared to 1 cm slice interval) was generated for 2-, 3-, and 4 cm slice intervals. L3 skeletal muscle index (SMI) was also calculated in 30 patients. RESULTS: Relative error increased with slice interval using the cylindrical (0.45 vs. 1.06 vs. 1.72%) and truncated cone equation (0.27 vs. 0.58 vs. 0.74%) for 2, 3, and 4 cm, respectively. Significantly, the cylindrical equation produced approximately twice the error compared to truncated cone, with 3 cm (0.58 vs. 1.06%, P < 0.01) and 4 cm intervals (0.74 vs. 1.72%, P < 0.001). Finally, quadriceps MV was significantly correlated to L3 SMI (r(2) = 0.44, P < 0.0001). CONCLUSION: The use of the truncated equation with a 4 cm slice interval on MRI offers an efficient but accurate estimation of quadricep muscle volume in ESLD patients

Childhood trauma may increase risk of psychosis and mood disorder in genetically high-risk children and adolescents by enhancing the accumulation of risk indicators

Background: Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk. Methods: We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring. Results: Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58). Conclusion: Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders

Concrete substrate moisture requirements for durable concrete repairs – a field study

peer reviewedIn concrete repair specifications, the required moisture condition of the substrate, which can play an important role for bond development, and, ultimately, on the long-term repair / overlay durability, is generally ill-defined and addressed without due consideration to the given substrate characteristics. The standard specification, if any, is to require saturated surface dry (SSD) condition of the substrate prior to application of cementitious repair materials, which is theoretically achieved after saturating the substrate and then letting the surface just start to dry out. This does provide an intuitive solution founded on rational considerations, but it has never really been precisely defined, measured, nor validated. The influence of substrate surface moisture on the bond between the existing concrete and the new repair material is an issue of significant importance. This paper revisits the question, in light of results from a project designed to develop guidelines for moisture conditioning of a concrete substrate prior to a cementitious repair, which was part of a larger effort to develop guidelines for surface preparation of concrete prior to repair. Over the course of the project, multiple series of test slabs were repaired after being subjected to different surface moisture conditioning and then tested for bond strength tests at different ages. The findings are discussed, together with those from previous studies, and recommendations are issued.9. Industry, innovation and infrastructur

Emergency Medicine Research Directors and Research Programs: Characteristics and Factors Associated with Productivity

: Background: Periodic surveys of research directors (RDs) in emergency medicine (EM) are useful to assess the specialty's development and evolution of the RD role. Objectives: To assess associations between characteristics and research productivity of RDs and EM programs. Methods: A survey of EM RDs was developed using the nominal group technique and pilot tested. RDs or surrogate respondents at programs certified by the Accreditation Council for Graduate Medical Education were contacted by e-mail in early 2005. The survey assessed programs' research infrastructure and productivity, as well as RD characteristics, responsibilities, and career satisfaction. Three measures of research productivity were empirically defined: research publications, grant awards, and grant revenue. Results: Responses were received from 86% of 123 EM programs. Productivity was associated with the presence of nonclinical faculty, dedicated research coordinators, and reduced clinical hours for research faculty. Programs with an RD did not have greater research productivity, using any measure, than those without an RD. The majority of RDs cited pursuing their own studies, obtaining funding, research mentoring, and research administration to be major responsibilities. The majority characterized internal research funding, grant development support, and support from other faculty as inadequate. Most RDs are satisfied with their careers and expect to remain in the position for three or more years. Conclusions: Research productivity of EM residency programs is associated with the presence of dedicated research faculty and staff and with reduced clinical demands for research faculty. Despite perceiving deficiencies in important resources, most RDs are professionally satisfied.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72908/1/j.aem.2006.01.027.pd

A Multi-national Pooled Analysis of 434 Cases of Stage I Non-small Cell Lung Cancer (NSCLC) Treated with Volumetrically Image-guided Stereotactic Lung Radiotherapy: Results from the Elekta Collaborative Lung Research Group

Background: Published lung SBRT outcomes/dose response data for inoperable NSCLC come from small phase I-II studies or larger datasets not requiring image-guided radiotherapy (IGRT) or volumetric prescriptions. This entire cohort of SBRT patients had daily online cone-beam CT. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C