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Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well‐characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune‐related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor‐infiltrating leukocytes and circulating T cells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

Abstract Objective To compare the success of establishing spontaneous micturition following immediate trial without catheter (TWOC) to delayed TWOC in males catheterized for acute urinary retention. Materials and methods In this systematic review, we included studies reporting success rates of immediate TWOC or delayed TWOC (≤30 days) among males ≥18 years of age catheterized for acute urinary retention. We excluded studies on suprapubic catheterization, postoperative/perioperative catheterization and urinary retention related to trauma. We searched the following databases: MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Open Grey and Clinicaltrials.gov. The search was concluded on 30 November 2022. There were no restrictions on language or publication date. Risk of bias was assessed using the ROB 2.0 and ROBINS‐I tools. We did random‐effects restricted maximum likelihood model meta‐analyses. Certainty of evidence was assessed using GRADE. Results We included 61 studies. In two randomized controlled trials (RCTs), both with some concerns for risk of bias, including in total 174 participants, the relative success rate was 1.22 (95% CI 0.84–1.76) favouring delayed TWOC. In two comparative cohort studies, both with serious risk of bias, including 642 participants, the relative success rate was 1.18 (0.94–1.47) favouring delayed TWOC. One study was excluded from this meta‐analysis because of critically low quality. Four studies reporting success rates for cohorts with immediate TWOC, all with serious risk of bias, including 409 participants, had an overall success rate of 47% (29–66). Fifty‐two studies reporting success rates for cohorts with delayed TWOC, all with serious risk of bias, including 12 489 participants, had an overall success rate of 53% (49–56). The certainty of the evidence was considered low for the RCTs and very low for the rest. Conclusion There was a limited number of appropriately designed studies addressing the research question directly. The evidence favours neither approach.

BackgroundPatient education, hand exercises, and the use of assistive devices are recommended as first-line treatments for individuals with hand osteoarthritis (OA). However, the quality of care services for this patient group is suboptimal in primary care. ObjectiveThe overarching goal was to develop and evaluate feasibility of an app-based self-management intervention for people with hand OA. This feasibility study aims to assess self-reported usability and satisfaction, change in outcomes and quality-of-care, exercise adherence and patients’ experiences using the app. MethodsThe development and feasibility testing followed the first 2 phases of the Medical Research Council framework for the development and evaluation of complex interventions and were conducted in close collaboration with patient research partners (PRPs). A 3-month pre-post mixed methods design was used to evaluate feasibility. Men and women over 40 years of age diagnosed with painful, symptomatic hand OA were recruited. Usability was assessed using the System Usability Scale (0-100), while satisfaction, usefulness, pain, and stiffness were evaluated using a numeric rating scale (NRS score from 0 to 10). The activity performance of the hand was measured using the Measure of Activity Performance of the Hand (MAP-Hand) (1-4), grip strength was assessed with a Jamar dynamometer (kg), and self-reported quality of care was evaluated using the Osteoarthritis Quality Indicator questionnaire (0-100). Participants were deemed adherent if they completed at least 2 exercise sessions per week for a minimum of 8 weeks. Focus groups were conducted to explore participants’ experiences using the app. Changes were analyzed using a paired sample t test (mean change and 95% CI), with the significance level set at P

Background: Caring for a family member can be demanding, particularly when caregivers experience profound distress. Supportive interventions may help prevent mental and physical illness in the caregiver. General practice plays a key role by regularly engaging with patients and caregivers, thereby being able to identify their support needs, offer talk therapy and refer to care initiatives. Objective: This study aimed to develop and pilot-test the Caregiver Care Model to mitigate grief reactions among caregivers in general practice. Design: A participatory intervention development study. Methods: A prototype was developed in a workshop with healthcare professionals. The prototype was refined based on a pilot-test among 40 caregivers from 5 general practice clinics and a workshop with general practitioners. The data were obtained from workshops, feedback questionnaires completed by healthcare professionals, and interviews with caregivers and general practitioners. The analysis focused on model development and mechanisms of impact. Results: The prototype was refined by focusing the dialogue questionnaire, minimising the grief facilitation tools and expanding the target group. The prototype seemed to accommodate the needs among caregivers by acknowledging their situation. The final model includes up to seven caregiver consultations in general practice. A dialogue questionnaire filled in by the caregiver serves as a fixed starting point and preparation for the first consultation. If needed, talk therapy in general practice or referrals to other services are used. Conclusion: The model offers promising support for caregivers. Its flexible structure allows for customisation. The viability of the model should be further tested.

Abstract Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C. Depleting Odam and Cabs1 in this region prevents metastasis. Notably, the gene expression signatures, resulting from our study, predict progression-free and overall survival and distinguish primary and metastatic human prostate cancer. This study emphasizes positive genetic interactions between classical tumor suppressor genes and epigenetic modulators in metastatic PCa progression, offering insights into potential treatments.

Background: Venous thromboembolism (VTE) is the third leading cause of preventable hospital-associated (HA) death. Most HA-VTE, including fatal pulmonary emboli, occur among medically ill patients. The rate of symptomatic VTE more than doubles over the first 21 days after hospital discharge. Trials have demonstrated that the burden of HA-VTE may be reduced with postdischarge thromboprophylaxis; however, few patients receive this therapy. We formerly validated the ability of eVTE (eVTE is the abbreviation for a risk assessment tool constituted by 2 calculations: one predicts 90-day VTE and the other predicts 30-day major bleeding derived from only elements of the complete blood count and basic metabolic panel and age) to identify medical patients being discharged with both an elevated risk of VTE and a low risk of bleeding. Objectives: Implement a cluster-randomized, stepped wedge, type II hybrid implementation/effectiveness trial generating an alert among select at-risk patients upon discharge for implementation of thrombosis chemoprophylaxis in a 23-hospital not-for-profit healthcare system. Methods: We use the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to guide implementation and outcomes reporting. Results: The primary outcome for aim 1 (implementation) is the prescription of rivaroxaban 10 mg daily for 30 days as postdischarge thromboprophylaxis among at-risk patients. The primary efficacy and safety outcomes (effectiveness) are the 90-day composite of symptomatic VTE, myocardial infartcion, nonhemorrhagic stroke, all-cause mortality, and 30-day major bleeding. Conclusion: The eVTE trial will provide high-quality, real-world evidence on the effectiveness and safety of a pragmatic intervention to implement targeted postdischarge thromboprophylaxis using decision support embedded in the electronic health record.

Abstract Aim Our aim was to examine women's attitudes towards addressing and documenting sexual function in a Nordic gynaecological and obstetric outpatient setting. Materials and Methods We performed a cross‐sectional, anonymous survey amongst women referred to the gynaecological or obstetric outpatient clinic at the University Hospital in Trondheim, Norway. The women completed a written, self‐developed questionnaire with 10 questions. Results During a 5‐month period, 494 out of 700 distributed questionnaires were completed (response rate 71%). Of the participating women, 87% would accept that a gynaecologist routinely asked them about sexual function during an outpatient appointment. Significantly more women 40 years and older (postreproductive), compared to women below 40 years (reproductive) did not want to be asked about sexual function [a difference of 6.7% (95% confidence interval (CI): 0.6, 13)]. Between 90% and 98% of the women would also accept specific questions about problems with sexual desire, arousal, orgasm and pain during intercourse. Women were most likely to accept questions about pain during intercourse. More women in the postreproductive age group compared to women of reproductive age did not accept questions about desire [a difference of 6.2% (95% CI: 1.9, 11.5)], arousal [a difference of 6.4% (95% CI: 0.7, 12.6)] and orgasm [a difference of 5.4% (95% CI: 0, 11.5)]. Women attending different clinics or from different cultural backgrounds did not answer significantly differently. More than half of the respondents preferred a medical journal with restricted access for documentation for general information (52.9%) as well as for specific information (60.1%) on sexual function. There was a tendency for women from the Nordic countries, compared to women from other European countries, to prefer this information to be stored in the restricted medical record, while this response was similar for women of the postreproductive and reproductive age group, or for women attending different clinics. Conclusion The large majority of women in this study accept that the gynaecologist asks general and specific questions about sexual function. Just over half of the women preferred information about sexual function to be documented in a medical journal with restricted access.

The most common complication in older surgical patients is postoperative delirium (POD). POD is associated with preoperative cognitive impairment and longer durations of intraoperative burst suppression (BSup) – electroencephalography (EEG) with repeated periods of suppression (very low-voltage brain activity). However, BSup has modest sensitivity for predicting POD. We hypothesized that a brain state of lowered EEG power immediately precedes BSup, which we have termed “pre-burst suppression” (preBSup). Further, we hypothesized that even patients without BSup experience these preBSup transient reductions in EEG power, and that preBSup (like BSup) would be associated with preoperative cognitive function and delirium risk. Data included 83 32-channel intraoperative EEG recordings of the first hour of surgery from 2 prospective cohort studies of patients ≥age 60 scheduled for ≥2-h non-cardiac, non-neurologic surgery under general anesthesia (maintained with a potent inhaled anesthetic or a propofol infusion). Among patients with BSup, we defined preBSup as the difference in 3–35 Hz power (dB) during the 1-s preceding BSup relative to the average 3–35 Hz power of their intraoperative EEG recording. We then recorded the percentage of time that each patient spent in preBSup, including those without BSup. Next, we characterized the association between percentage of time in preBSup and (1) percentage of time in BSup, (2) preoperative cognitive function, and (3) POD incidence. The percentage of time in preBSup and BSup were correlated (Spearman’s ρ [95% CI]: 0.52 [0.34, 0.66], p < 0.001). The percentage of time in BSup, preBSup, or their combination were each inversely associated with preoperative cognitive function (β [95% CI]: −0.10 [−0.19, −0.01], p = 0.024; −0.04 [−0.06, −0.01], p = 0.009; −0.04 [−0.06, −0.01], p = 0.003, respectively). Consistent with prior literature, BSup was significantly associated with POD (odds ratio [95% CI]: 1.34 [1.01, 1.78], p = 0.043), though this association did not hold for preBSup (odds ratio [95% CI]: 1.04 [0.95, 1.14], p = 0.421). While all patients had ≥1 preBSup instance, only 20.5% of patients had ≥1 BSup instance. These exploratory findings suggest that future studies are warranted to further study the extent to which preBSup, even in the absence of BSup, can identify patients with impaired preoperative cognition and/or POD risk.

Immunotherapy has revolutionised cancer treatment. However, not all cancer patients benefit, and current stratification strategies based primarily on PD1 status and mutation burden are far from perfect. We hypothesised that high activation of an innate response relative to the adaptive response may prevent proper tumour neoantigen identification and decrease the specific anticancer response, both in the presence and absence of immunotherapy. To investigate this, we obtained transcriptomic data from three large publicly available cancer datasets, the Cancer Genome Atlas (TCGA), the Hartwig Medical Foundation (HMF), and a recently published cohort of metastatic bladder cancer patients treated with immunotherapy. To analyse immune infiltration into bulk tumours, we developed an RNAseq-based model based on previously published definitions to estimate the overall level of infiltrating innate and adaptive immune cells from bulk tumour RNAseq data. From these, the adaptive-to-innate immune ratio (A/I ratio) was defined. A meta-analysis of 32 cancer types from TCGA overall showed improved overall survival in patients with an A/I ratio above median (Hazard ratio (HR) females 0.73, HR males 0.86, P < 0.05). Of particular interest, we found that the association was different for males and females for eight cancer types, demonstrating a gender bias in the relative balance of the infiltration of innate and adaptive immune cells. For patients with metastatic disease, we found that responders to immunotherapy had a significantly higher A/I ratio than non-responders in HMF (P = 0.036) and a significantly higher ratio in complete responders in a separate metastatic bladder cancer dataset (P = 0.022). Overall, the adaptive-to-innate immune ratio seems to define separate states of immune activation, likely linked to fundamental immunological reactions to cancer. This ratio was associated with improved prognosis and improved response to immunotherapy, demonstrating potential relevance to patient stratification. Furthermore, by demonstrating a significant difference between males and females that associates with response, we highlight an important gender bias which likely has direct clinical relevance.

Background: Unicompartmental knee arthroplasty (UKA) treats arthritis involving only one compartment of the knee. Lateral UKA is mainly performed through medial parapatellar or lateral parapatellar approaches to the knee. This technique article introduces a medial subvastus approach to lateral UKA, discusses the clinical rationale behind its use, and offers a preliminary retrospective study on short-term outcomes of lateral UKAs using the lateral vs medial subvastus approaches. Methods: A description of the medial subvastus approach is included. In addition, we reviewed 32 and 30 lateral UKAs performed using the lateral and medial subvastus approaches, respectively. Minimum follow-up duration was 1 year. Knee injury and osteoarthritis outcome score for joint replacement (KOOS, JR) knee scores were used for comparison. Results: Age and body mass index were similar between the 2 cohorts. Mean KOOS, JR. scores for the subvastus approach group were significantly higher than those for the lateral approach group at 81.41 ± 2.0 for medial subvastus and 74.19 ± 2.9 for lateral (P = .02). One deep infection and 2 revision total knee arthroplasties occurred in the lateral approach group. Neither occurred in the subvastus group. The mean follow-up duration was significantly longer for the lateral approach group than that for the subvastus group at 749 vs 410 days (P < .001). Literature on time-dependence of patient-reported outcomes supports usage of the data, despite follow-up discrepancies. Conclusions: A subvastus approach for lateral UKA may offer improved visualization, easier conversion to total knee arthroplasty, and faster recovery, based on clinical observation. Preliminary results suggest improved short-term knee scores compared to a lateral approach.

Introduction There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS. Objectives This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS. Methods Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS. Conclusions Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance. Disclosure DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp

Abstract Background To assess the agreement of continuous measurements between a number of observers, Jones et al. introduced limits of agreement with the mean (LOAM) for multiple observers, representing how much an individual observer can deviate from the mean measurement of all observers. Besides the graphical visualisation of LOAM, suggested by Jones et al., it is desirable to supply LOAM with confidence intervals and to extend the method to the case of multiple measurements per observer. Methods We reformulate LOAM under the assumption the measurements follow an additive two-way random effects model. Assuming this model, we provide estimates and confidence intervals for the proposed LOAM. Further, this approach is easily extended to the case of multiple measurements per observer. Results The proposed method is applied on two data sets to illustrate its use. Specifically, we consider agreement between measurements regarding tumour size and aortic diameter. For the latter study, three measurement methods are considered. Conclusions The proposed LOAM and the associated confidence intervals are useful for assessing agreement between continuous measurements.

The dihydroazulene/vinylheptafulvene (DHA/VHF) thermocouple is a promising candidate for thermal heat batteries that absorb and store solar energy as chemical energy without the need for insulation. However, in order to be viable the energy storage capacity and lifetime of the high energy form (i.e., the free energy barrier to the back reaction) of the canonical parent compound must be increased significantly to be of practical use. We use semiempirical quantum chemical methods, machine learning, and density functional theory to virtually screen over 230 billion substituted DHA molecules to identify promising candidates. We identify a molecule with a predicted energy density of 0.38 kJ/g, which is significantly larger than the 0.14 kJ/g computed for the parent compound. The free energy barrier to the back reaction is 11 kJ/mol higher than the parent compound, which should correspond to a half-life of about 10 days—4 months. This is considerably longer than the 3–39 h (depending on solvent) observed for the parent compound and sufficiently long for many practical applications. Our paper makes two main important contributions: (1) a novel and generally applicable methodological approach that makes screening of huge libraries for properties involving chemical reactivity with modest computational resources, and (2) a clear demonstration that the storage capacity of the DHA/VHF thermocouple cannot be increased to >0.5 kJ/g by combining simple substituents.

The specific role of the autonomic nervous system (ANS) in emotional and behavioral regulation—particularly in relation to automatic processes—has gained increased attention in the sensory modulation literature. This mini-review article summarizes current knowledge about the role of the ANS in sensory modulation, with a focus on the integrated functions of the ANS and the hypothalamic-pituitary-adrenal (HPA) axis and their measurement. Research from the past decade illustrates that sympathetic and parasympathetic interactions are more complex than previously assumed. Patterns of ANS activation vary across individuals, with distinct physiological response profiles influencing the reactivity underlying automatic behavioral responses. This review article advances a deeper understanding of stress and the complex stress patterns within the ANS and HPA axis that contribute to allostatic load (AL). We argue that using multiple physiological measurements to capture individual ANS response variation is critical for effectively treating children with sensory modulation disorder (SMD) and sensory differences. We consider the relative contributions of automatic vs. deliberately controlled processes across large-scale neural networks in the development of sensorimotor function and their associated links with arousal patterns and sensory over- and under-responsivity.

The identification and use of structure–property relationships lies at the heart of the chemical sciences. Quantum mechanics forms the basis for the unbiased virtual exploration of chemical compound space (CCS), imposing substantial compute needs if chemical accuracy is to be reached. In order to accelerate predictions of quantum properties without compromising accuracy, our lab has been developing quantum machine learning (QML) based models which can be applied throughout CCS. Here, we briefly explain, review, and discuss the recently introduced operator formalism which substantially improves the data efficiency for QML models of common response properties.

Abstract Background The mechanisms underlying the association of parental socioeconomic position with later life allostatic load remain unclear. The present study aims to examine potential pathways underlying this association: personality, social relations, intelligence and education. Methods The study comprised 361 members of the Copenhagen Perinatal Cohort who participated in two subsequent follow-ups: the Prenatal Development Project (mean age 27 years) and the Copenhagen Aging and Midlife Biobank study (mean age 50 years). Allostatic load was based on 14 biomarkers representing the inflammatory, metabolic and cardiovascular system measured at midlife. Information on potential mediators was collected in young adulthood, and their role in the association of parental socioeconomic position with midlife allostatic load were examined in linear regression path analyses. Results Parental socioeconomic position at one year was inversely associated with midlife allostatic load (β = − 0.238, p

Nitrous oxide (N2O) is an important and strong greenhouse gas in the atmosphere. It is produced by microbes during nitrification and denitrification in terrestrial and aquatic ecosystems. The main sinks for N2O are turnover by denitrification and photolysis and photo-oxidation in the stratosphere. In the linear N = N = O molecule 15N substitution is possible in two distinct positions: central and terminal. The respective molecules, 14N15N16O and 15N14N16O, are called isotopomers. It has been demonstrated that N2O produced by nitrifying or denitrifying microbes exhibits a different relative abundance of the isotopomers. Therefore, measurements of the site preference (difference in the abundance of the two isotopomers) in N2O can be used to determine the source of N2O, i.e., nitrification or denitrification. Recent instrument development allows for continuous position-dependent δ15N measurements at N2O concentrations relevant for studies of atmospheric chemistry. We present results from continuous incubation experiments with denitrifying bacteria, Pseudomonas fluorescens (producing and reducing N2O) and Pseudomonas chlororaphis (only producing N2O). The continuous measurements of N2O isotopomers reveals the transient isotope exchange among KNO3, N2O, and N2. We find bulk isotopic fractionation of −5.01 ‰ ± 1.20 for P. chlororaphis, in line with previous results for production from denitrification. For P. fluorescens, the bulk isotopic fractionation during production of N2O is −52.21 ‰ ± 9.28 and 8.77 ‰ ± 4.49 during N2O reduction.The site preference (SP) isotopic fractionation for P. chlororaphis is −3.42 ‰ ± 1.69. For P. fluorescens, the calculations result in SP isotopic fractionation values of 5.73 ‰ ± 5.26 during production of N2O and 2.41 ‰ ± 3.04 during reduction of N2O. In summary, we implemented continuous measurements of N2O isotopomers during incubation of denitrifying bacteria and believe that similar experiments will lead to a better understanding of denitrifying bacteria and N2O turnover in soils and sediments and ultimately hands-on knowledge on the biotic mechanisms behind greenhouse gas exchange of the globe.

We present a workflow for efficient construction and calibration of large-scale groundwater models that includes the integration of airborne electromagnetic (AEM) data and hydrological data. In the first step, the AEM data are inverted to form a 3-D geophysical model. In the second step, the 3-D geophysical model is translated, using a spatially dependent petrophysical relationship, to form a 3-D hydraulic conductivity distribution. The geophysical models and the hydrological data are used to estimate spatially distributed petrophysical shape factors. The shape factors primarily work as translators between resistivity and hydraulic conductivity, but they can also compensate for structural defects in the geophysical model. The method is demonstrated for a synthetic case study with sharp transitions among various types of deposits. Besides demonstrating the methodology, we demonstrate the importance of using geophysical regularization constraints that conform well to the depositional environment. This is done by inverting the AEM data using either smoothness (smooth) constraints or minimum gradient support (sharp) constraints, where the use of sharp constraints conforms best to the environment. The dependency on AEM data quality is also tested by inverting the geophysical model using data corrupted with four different levels of background noise. Subsequently, the geophysical models are used to construct competing groundwater models for which the shape factors are calibrated. The performance of each groundwater model is tested with respect to four types of prediction that are beyond the calibration base: a pumping well's recharge area and groundwater age, respectively, are predicted by applying the same stress as for the hydrologic model calibration; and head and stream discharge are predicted for a different stress situation. As expected, in this case the predictive capability of a groundwater model is better when it is based on a sharp geophysical model instead of a smoothness constraint. This is true for predictions of recharge area, head change, and stream discharge, while we find no improvement for prediction of groundwater age. Furthermore, we show that the model prediction accuracy improves with AEM data quality for predictions of recharge area, head change, and stream discharge, while there appears to be no accuracy improvement for the prediction of groundwater age.

La optimización de la producción y la calidad de carne son los principales objetivos de los productores y del sector comercial de la carne. Actualmente la producción de animales de engorde a corral presenta una buena eficiencia productiva. Asimismo, en Argentina una nueva categoría de animales, machos enteros jóvenes, ha sido recientemente implementada, presentado interés e inquietud por parte de los productores y la industria de la carne. Desde el punto de vista de la tecnología de los alimentos es interesante estudiar e investigar los parámetros fisicoquímicos y reológicos que ayuden a explicar la presencia/ausencia de cambios sobre la calidad de la carne. El objetivo de este estudio fue evaluar la calidad de la carne y las características térmicas del tejido conectivo en animales alimentados a corral, castrados versus no castrados. La ausencia de testosterona, esperable en machos castrados, no produjo diferencias significativas en la calidad de carne respecto al grupo no castrado. El color, las pérdidas por cocción y la terneza resultaron equivalentes entre ambos grupos de animales. Sin embargo la respuesta de la contracción máxima generada por el tejido conectivo perimisio del músculo LD durante el tratamiento térmico mostró diferencias significativas entre los grupos. Además la fuerza de contracción máxima también varió entre los perimisios musculares LD, ST y PP de animales castrados mientras no así la temperatura de inicio de la contracción (Tonset). Los resultados indicarían la posibilidad de que la ausencia de testosterona afecte de manera diferente la síntesis de tejido conectivo intramuscular in vivo en los diferentes músculos. Al respecto, se requerirán nuevas investigaciones que profundicen estos hallazgos.

Abstract Introduction Despite the understanding of allostatic load (AL) as a consequence of ongoing adaptation to stress, studies of the stress–AL association generally focus on a narrow conceptualization of stress and have thus far overlooked potential confounding by personality. The present study examined the cross‐sectional association of objective and subjective stress with AL, controlling for Big Five personality traits. Methods Participants comprised 5,512 members of the Copenhagen Aging and Midlife Biobank aged 49–63 years (69% men). AL was measured as a summary index of 14 biomarkers of the inflammatory, cardiovascular, and metabolic system. Objective stress was assessed as self‐reported major life events in adult life. Subjective stress was assessed as perceived stress within the past four weeks. Results Both stress measures were positively associated with AL, with a slightly stronger association for objective stress. Adjusting for personality traits did not significantly change these associations. Conclusions The results suggest measures of objective and subjective stress to have independent predictive validity in the context of personality. Further, it is discussed how different operationalizations of stress and AL may account for some of the differences in observed stress–AL associations.

In spite of geophysics being used increasingly, it is often unclear how and when the integration of geophysical data and models can best improve the construction and predictive capability of groundwater models. This paper uses a newly developed HYdrogeophysical TEst-Bench (HYTEB) that is a collection of geological, groundwater and geophysical modeling and inversion software to demonstrate alternative uses of electromagnetic (EM) data for groundwater modeling in a hydrogeological environment consisting of various types of glacial deposits with typical hydraulic conductivities and electrical resistivities covering impermeable bedrock with low resistivity (clay). The synthetic 3-D reference system is designed so that there is a perfect relationship between hydraulic conductivity and electrical resistivity. For this system it is investigated to what extent groundwater model calibration and, often more importantly, model predictions can be improved by including in the calibration process electrical resistivity estimates obtained from TEM data. In all calibration cases, the hydraulic conductivity field is highly parameterized and the estimation is stabilized by (in most cases) geophysics-based regularization. For the studied system and inversion approaches it is found that resistivities estimated by sequential hydrogeophysical inversion (SHI) or joint hydrogeophysical inversion (JHI) should be used with caution as estimators of hydraulic conductivity or as regularization means for subsequent hydrological inversion. The limited groundwater model improvement obtained by using the geophysical data probably mainly arises from the way these data are used here: the alternative inversion approaches propagate geophysical estimation errors into the hydrologic model parameters. It was expected that JHI would compensate for this, but the hydrologic data were apparently insufficient to secure such compensation. With respect to reducing model prediction error, it depends on the type of prediction whether it has value to include geophysics in a joint or sequential hydrogeophysical model calibration. It is found that all calibrated models are good predictors of hydraulic head. When the stress situation is changed from that of the hydrologic calibration data, then all models make biased predictions of head change. All calibrated models turn out to be very poor predictors of the pumping well's recharge area and groundwater age. The reason for this is that distributed recharge is parameterized as depending on estimated hydraulic conductivity of the upper model layer, which tends to be underestimated. Another important insight from our analysis is thus that either recharge should be parameterized and estimated in a different way, or other types of data should be added to better constrain the recharge estimates.

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD.

Scalable quantum information processing will require quantum networks of qubits with the ability to coherently transfer quantum states between the desired sender and receiver nodes. Here we propose a scheme to implement a quantum router that can direct quantum states from an input qubit to a preselected output qubit. The path taken by the transferred quantum state is controlled by the state of one or more ancilla qubits. This enables directed transport between a sender and a number of receiver nodes, as well as generation of distributed entanglement in the network. We demonstrate the general idea using a two-output setup and discuss how the quantum routing may be expanded to several outputs. We also present a possible realization of our ideas with superconducting circuits.