Evaluation of an Electrolyte Analyser for Measurement of Concentrations of Ionized Calcium and Magnesium in Cats

The goal of this study was to evaluate the Nova CRT 8 electrolyte analyser for determination of concentrations of ionized calcium (Cai) and magnesium (Mgi) in cats, todetermine the effects of sample handling and storage and to establish reference ranges. The precision and analytical accuracy of the Nova CRT 8 analyser were good. The concentrations of Cai and Mgi were significantly lower in aerobically handled serum samples than in those handled anaerobically. The concentrations of Cai and Mgi differed significantly among whole blood, plasma and serum. In anaerobically handled serum, the concentration of Cai was stable for 8 h at 22°C, for 5 days at 4°C and for 1 week at −20°C. The concentration of Mgi was stable for 4 h at 22°C but for less than 24 h at 4°C and for less than 1 week at −20°C. In serum from 36 cats, the reference ranges were 1.20-1.35 mmol/L for Cai and 0.47-0.59 mmol/L for Mgi. The Nova CRT 8 electrolyte analyser is suitable for determination of Cai and Mgi concentrations in cats. Anaerobically handled serum samples are recommended and, stored at room temperature, they yield accurate results when analysed within 4

Therapeutic Value of Drugs Granted Accelerated Approval or Conditional Marketing Authorization in the US an Europe From 2007 to 2021

IMPORTANCE: The number of drugs approved through the accelerated approval or conditional marketing authorization pathways has increased with unclear evidence of their therapeutic value. OBJECTIVES: To assess the therapeutic value of drug indications granted accelerated approval in the US or conditional marketing authorization in the European Union (EU) overall and for cancer indications. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the public databases of the US Food and Drug Administration and the European Medicines Agency to identify all drugs (initial and supplemental indications) granted accelerated approval in the US or conditional marketing authorization (initial indications only) in the EU between January 1, 2007, and December 31, 2021. Therapeutic value ratings were obtained from national health authorities in Germany, France, and Canada. MAIN OUTCOMES AND MEASURES: Descriptive statistics were used to assess the proportion of accelerated approvals and conditional marketing authorizations overall and for cancer vs noncancer indications rated as having high added therapeutic value. RESULTS: The cohort included 146 drug indications (94 first indications, 52 supplemental indications) in the US and 58 (all first indications) in the EU. Most drugs were approved for cancer (122 [83.6%] in the US; 40 [69.0%] in the EU). Therapeutic value ratings were available for 90 drug indications (61.6%) in the US and 56 (96.6%) in the EU. Overall, 35 drug indications granted accelerated approval (38.9%) and 21 granted conditional marketing authorization (37.5%) had high added therapeutic value in the US and EU, respectively, at the time of approval. The proportions of indications rated as having high added therapeutic value were 36.0% (27 of 75) for cancer vs 53.3% (8 of 15) for noncancer indications in the US and 30.8% (12 of 39) for cancer vs 52.9% (9 of 17) for noncancer indications in the EU. CONCLUSIONS AND RELEVANCE: In this cohort study, among new drug indications approved through the accelerated approval or conditional marketing authorization pathways in the US and Europe from 2007 to 2021, 38.9% and 37.5%, respectively, demonstrated high therapeutic value. A substantially lower proportion of cancer indications than noncancer indications were rated as having high therapeutic value. Policy makers and regulators should increase enforcement of timely postapproval study completion for drugs qualifying for these pathways

Gluon fusion into Higgs pairs at NLO QCD and the top mass scheme

We present the calculation of the full next-to-leading order (NLO) QCD corrections to Higgs boson pair production via gluon fusion at the LHC, including the exact top-mass dependence in the two-loop virtual and one-loop real corrections. This is the first independent cross-check of the NLO QCD corrections presented in the literature before. Our calculation relies on numerical integrations of Feynman integrals, stabilised with integration-by-parts and a Richardson extrapolation to the narrow width approximation. We present results for the total cross section as well as for the invariant Higgs-pair-mass distribution at the LHC, including for the first time a study of the uncertainty due to the scheme and scale choice for the top mass in the loops

Full NLO QCD predictions for Higgs-pair production in the 2-Higgs-doublet model

After the discovery of the Higgs boson in 2012 at the CERN Large Hadron Collider (LHC), the study of its properties still leaves room for an extended Higgs sector with more than one Higgs boson. 2-Higgs doublet models (2HDMs) are well-motivated extensions of the Standard Model (SM) with five physical Higgs bosons: two CP-even states h and H, one CP-odd state A, and two charged states $H^{\pm}$. In this letter, we present the calculation of the full next-to-leading order (NLO) QCD corrections to hH and AA production at the LHC in the 2HDM at small values of the ratio of the vacuum expectation values, $tan\space\beta$, including the exact top-mass dependence everywhere in the calculation. Using techniques applied in the NLO QCD SM Higgs pair production calculation, we present results for the total cross section as well as for the Higgs-pair-mass distribution at the LHC. We also provide the top-quark scale and scheme uncertainties which are found to be sizeable

Transfer-matrix scaling from disorder-averaged correlation lengths for diluted Ising systems

A transfer matrix scaling technique is developed for randomly diluted systems, and applied to the site-diluted Ising model on a square lattice in two dimensions. For each allowed disorder configuration between two adjacent columns, the contribution of the respective transfer matrix to the decay of correlations is considered only as far as the ratio of its two largest eigenvalues, allowing an economical calculation of a configuration-averaged correlation length. Standard phenomenological-renormalisation procedures are then used to analyse aspects of the phase boundary which are difficult to assess accurately by alternative methods. For magnetic site concentration $p$ close to $p_c$, the extent of exponential behaviour of the $T_c \times p$ curve is clearly seen for over two decades of variation of $p - p_c$. Close to the pure-system limit, the exactly-known reduced slope is reproduced to a very good approximation, though with non-monotonic convergence. The averaged correlation lengths are inserted into the exponent-amplitude relationship predicted by conformal invariance to hold at criticality. The resulting exponent $\eta$ remains near the pure value (1/4) for all intermediate concentrations until it crosses over to the percolation value at the threshold.Comment: RevTeX 3, 11 pages +5 figures, uuencoded, to appear in Phys. Rev. B (1994), PUC/RJ preprin

The impact of disease severity on the psychological well-being of youth affected by an inborn error of metabolism and their families: A one-year longitudinal study.

Inborn errors of metabolism (IEMs) refer to rare heterogeneous genetic disorders with various clinical manifestations that can cause serious physical and psychological sequelae. Results of previous studies on the impact of an IEM on health-related quality of life (HR-QoL) were incongruent and only few studies considered more broadly the psychological well-being of children with IEM and their families. Our objectives were to examine: (1) the impact of the IEM severity on the HR-QoL and psychological functioning of patients and their parents at baseline; and (2) its evolution over time; and (3) the correlation between parental and children's perspectives. Methods: The sample included 69 pediatric patients (mean age = 7.55 y, SD = 4.59) with evaluations at baseline and after one year. We collected data on HR-QoL, child mental health and emotional regulation as well as on parental mood and stress using different validated questionnaires. IEM severity was rated by a clinician through the biological subdomain of the pediatric INTERMED instrument. Results: Two groups of patients based on IEM severity scores were created (n = 31 with low and n = 38 with moderate/high IEM severity). The two groups differed with respect to age, diet and supplement intake. IEM severity had an impact on HR-QoL and behavioral symptoms in children, as well as on HR-QoL and stress in parents. For patients with moderate/high IEM severity, child and parental HR-QoL improved after 1-year of follow-up. We did not observe any significant difference between evaluations by patients versus parents. Conclusions: Our findings demonstrate that moderate/high IEM severity altered child and parental psychological well-being, but also revealed a significant improvement after one-year follow-up. This observation suggests that patients with a moderate/high IEM severity and their families benefit from the care of an interdisciplinary team including a child psychologist specialized in IEMs. Moreover, in patients with higher IEM severity there may also be more room for improvement compared to patients with low IEM severity. Future studies should focus on observations over a larger time span, particularly during adolescence, and should include objective measurements

Pathology and advanced imaging – characterization of a congenital cardiac defect and complex hemodynamics in a pig: A case report

Domestic pigs are widely used in cardiovascular research as the porcine circulatory system bears a remarkable resemblance to that of humans. In order to reduce variability, only clinically healthy animals enter the study as their health status is assessed in entry examination. Like humans, pigs can also suffer from congenital heart disease, such as an atrial septal defect (ASD), which often remains undetected. Due to the malformation of the endocardial cushion during organ development, mitral valve defects (e.g., mitral clefts) are sometimes associated with ASDs, further contributing to hemodynamic instability. In this work, we report an incidental finding of a hemodynamically highly relevant ASD in the presence of incompetent mitral and tricuspid valves, in an asymptomatic, otherwise healthy juvenile pig. In-depth characterization of the cardiac blood flow by four-dimensional (4D) flow magnetic resonance imaging (MRI) revealed a prominent diastolic left-to-right and discrete systolic right-to-left shunt, resulting in a pulmonary-to-systemic flow ratio of 1.8. Severe mitral (15 mL/stroke) and tricuspid (22 mL/stroke) regurgitation further reduced cardiac output. Pathological examination confirmed the presence of an ostium primum ASD and found a serous cyst of lymphatic origin that was filled with clear fluid partially occluding the ASD. A large mitral cleft was identified as the most likely cause of severe regurgitation, and histology showed mild to moderate endocardiosis in the coaptation area of both atrio-ventricular valves. In summary, although not common, congenital heart defects could play a role as a cause of experimental variability or even intra-experimental mortality when working with apparently heathy, juvenile pigs

Families With Violence Exposure and the Intergenerational Transmission of Somatization

Introduction: Adults who have histories of childhood trauma have been noted to display greater somatization, dissociative symptoms and affect dysregulation. What happens in the parent-child relationship when those traumatized children become parents? A potential link to somatization in the child has been suggested by several prior studies. Children who have early attachment disturbances had more physical complaints if their mothers displayed less maternal sensitivity during observed parent-child interactions. Yet, the intergenerational link between maternal and child somatization has not been sufficiently explored in a longitudinal study in order to understand the potential impact of maternal trauma history and related psychopathology on subsequent child somatization and psychopathology. Methods: This paper examined prospective, longitudinal data of 64 mother-toddler dyads (mean age = 2.4 years, SD = 0.7) who were later studied when children had a mean age of 7 years. Mothers with and without histories of interpersonal violence (IPV; physical/sexual abuse and/or family violence exposure) were included. Mothers with IPV histories were oversampled. Linear and Poisson regression models were used to test the associations between maternal IPV-related post-traumatic stress disorder (PTSD) with maternal somatization severity when children were toddlers, and between maternal somatization and maternal interactive behaviors with child somatization by maternal report and clinician-rated assessment at school-age. Results: Maternal PTSD severity was significantly associated with increased maternal somatization severity (p = 0.031). Maternal somatization severity during the child's early childhood predicted both maternal report of child somatization (p = 0.011) as well as child thought problems (p = 0.007) when children were school-aged. No association was found between maternal somatization and child-reported psychopathology. The study did not find that maternal alexithymia, caregiving behaviors or child exposure to violence contributed significantly to the model examining the association between maternal and child somatization. Conclusion: The results are in line with the hypothesis of intergenerational transmission of somatization in the context of IPV and related maternal PTSD during formative early development. We interpret this as an expression of psychological distress from mother to child, as maternal trauma and pathology affect the caregiving environment and, thus, the parent-child relationship. The authors conclude with a discussion of implications for parent-infant and early childhood intervention

Adherence to dietary recommendations is not associated with depression in two Swiss population-based samples.

Little is known about adherence to dietary recommendations and depression. Furthermore, dietary habits may differ among depression subtypes, which has not been evaluated previously. Two population-based Swiss studies, including 3620 individuals from PsyCoLaus and 11,032 individuals from the Swiss Health Survey 2012 (SHS), were used to examine the associations between adherence to common dietary guidelines and odds of depressive disorders. In both studies, depression was assessed by validated instruments. Adherence to dietary recommendations were assessed by a semi-quantitative food frequency questionnaire (PsyCoLaus) and by single item questions (SHS). Logistic regression analyses were used to assess the association of adhering to dietary recommendations with depression. For the analyses of diet with depression subtypes maximum-likelihood multinomial (polytomous) logistic regression analyses were conducted. No association of adherence to dietary recommendations with current major depressive disorder (MDD) was observed in any of the two study populations except for adherence to fish consumption, which was positively associated with MDD in the SHS. For depression subtypes, statistically significantly positive associations of vegetable consumption and adherence to the 5-a-day recommendation with current unspecified and current melancholic MDD were found. In conclusion, we don't see consistent associations between adherence to dietary recommendations and MDD or subtypes of depression