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In this paper, we report, for the first time to our knowledge, a new versatile and future proof diagnostic platform for diverse applications and heterogeneous biological targets. This platform relies on a plasmonic-augmented silicon photonic biochip to detect bacteria and protein biomarkers within minutes. To demonstrate the potential of this platform in diverse applications, we demonstrate the detection of two heterogeneous targets, the bacterium Escherichia coli (E. coli) and the molecule C-reactive protein (CRP) using a universal detection method. E. coli is one of the most commonly encountered bacterial pathogens involved in food monitoring, food born infections and water contamination applications, while CRP is a well-established disease severity indicator frequently used in common clinical practice. The biochip used is fully compatible with CMOS semiconductor manufacturing, while it hosts biosensors arrays for any combination of detection assays. Each biosensor exploits a 70 μm long aluminum plasmonic transducer within a silicon nitride waveguide-based Mach–Zehnder Interferometer. Each aluminum surface was silanized and biomodified with specific antibodies. Biosensing experiments revealed that CRP can be detected in diverse sample mediums, and E. coli detection was achieved in buffer at concentrations as low as 10 cells/ml within 13–25 min. The results are in good agreement with preceding numerical simulations. The modular nature of the reported biosensing platform makes it scalable and customizable, allowing nearly any combination of diagnostic tests targeting pathogens and proteins to be integrated on the same biochip for food quality monitoring, environmental monitoring, drug discovery and modern cell therapy manufacturing, or biomedical applications.

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a shift of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

Emerging evidence in women supports the notion that pregnancy may reset disease resistance, thereby providing protection against subsequent adverse health outcomes, but this hypothesis has not been adequately explored in domestic dogs. Cranial cruciate ligament (CCL) rupture is a degenerative orthopedic disease that frequently affects pet dogs, and its risk has been associated with disruption of the reproductive hormone axis. Our research team is conducting a lifetime cohort study of purebred Rottweilers in North America that have lived 30% longer than breed-average. Detailed medical and reproductive histories of 33 nulliparous and 32 parous Rottweilers were generated from questionnaires and review of medical records. Interviews with owners of bitches in the nulliparous group served to limit selection bias, confirming that in no instance was the reason for nulliparity based upon the owner’s suspicion that a bitch had a heightened risk for CCL rupture. The risk of CCL rupture associated with parity and other exposure variables was estimated using multivariate logistic regression. Overall, CCL rupture was diagnosed in 17 of 65 (26%) bitches. Median age at first litter and CCL rupture were 3.6 and 6.5 years, respectively. Compared to nulliparous, parous bitches had a significant 94% reduction in CCL rupture risk adjusted for duration of ovary exposure, overweight body condition, dietary pattern, habitual physical activity, and work/sport activity [ORadjusted (95% CI) = 0.06 (0.01–0.46); (p = 0.006)]. The observed parity-associated CCL rupture risk reduction remained robust in sensitivity analysis excluding six nulliparous bitches for which decision not to breed was based on diagnosis of hip or elbow dysplasia, conditions which may be genetically linked to CCL rupture [ORadjusted (95% CI) = 0.08 (0.01–0.58); (p = 0.01)]. This work sets the stage for replication studies in other canine populations that should begin to explore the mechanistic basis for parity-associated CCL rupture risk reduction and to pursue other non-reproductive health outcomes in bitches whose incidence or severity may be parity-sensitive.

ABSTRACT BACKGROUND: Hepatic retransplantation is associated with higher morbidity and mortality when compared to primary transplantation. Given the scarcity of organs and the need for efficient allocation, evaluating parameters that can predict post-retransplant survival is crucial. AIMS: This study aimed to analyze prognostic scores and outcomes of hepatic retransplantation. METHODS: Data on primary transplants and retransplants carried out in the state of Paraná in 2019 and 2020 were analyzed. The two groups were compared based on 30-day survival and the main prognostic scores of the donor and recipient, namely Model for End-Stage Liver Disease (MELD), MELD-albumin (MELD-a), Donor MELD (D-MELD), Survival Outcomes Following Liver Transplantation (SOFT), Preallocation Score to Predict Survival Outcomes Following Liver Transplantation (P-SOFT), and Balance of Risk (BAR). RESULTS: A total of 425 primary transplants and 30 retransplants were included in the study. The main etiology of hepatopathy in primary transplantation was ethylism (n=140; 31.0%), and the main reasons for retransplantation were primary graft dysfunction (n=10; 33.3%) and hepatic artery thrombosis (n=8; 26.2%). The 30-day survival rate was higher in primary transplants than in retransplants (80.5% vs. 36.7%, p=0.001). Prognostic scores were higher in retransplants than in primary transplants: MELD 30.6 vs. 20.7 (p=0.001); MELD-a 31.5 vs. 23.5 (p=0.001); D-MELD 1234.4 vs. 834.0 (p=0.034); SOFT 22.3 vs. 8.2 (p=0.001); P-SOFT 22.2 vs. 7.8 (p=0.001); and BAR 15.6 vs. 8.3 (p=0.001). No difference was found in terms of Donor Risk Index (DRI). CONCLUSIONS: Retransplants exhibited lower survival rates at 30 days, as predicted by prognostic scores, but unrelated to the donor’s condition.

Chronic limb-threatening ischemia (CLTI) causes significant morbidity with profound negative effects on health-related quality of life. As the prevalence of peripheral artery disease and diabetes continue to rise in our aging population, the public health impact of CLTI has escalated. Patient-reported outcome measures (PROMs) have become common and important measures for clinical evaluation in both clinical care and research. PROMs are important for the measurement of clinical effectiveness and cost effectiveness and for shared decision-making on treatment options. However, the PROMs used to describe the experience of patients with CLTI are heterogeneous, incomplete, and lack specific applicability to the underlying disease processes and diverse populations. For example, certain PROMs exist for patients with extremity wounds, and other PROMs exist for patients with pain, and still others exist for patients with vascular disease. Despite this multiplicity of tools, no single PROM encompasses all of the components necessary to describe the experiences of patients with CLTI. This significant unmet need is evident from both published reports and contemporary large-scale clinical trials in the field. In this systematic review, we review the current use of PROMs for patients with CLTI in clinical practice and in research trials and highlight the gaps that need to be addressed to develop a unifying PROM instrument for CLTI.

In this paper, we study both theoretically and experimentally the sensitivity of bimodal interferometric sensors where interference occurs between two plasmonic modes with different properties propagating in the same physical waveguide. In contrast to the well-known Mach–Zehnder interferometric (MZI) sensor, we show for the first time that the sensitivity of the bimodal sensor is independent of the sensing area length. This is validated by applying the theory to an integrated plasmo-photonic bimodal sensor that comprises an aluminum (Al) plasmonic stripe waveguide co-integrated between two accessible SU-8 photonic waveguides. A series of such bimodal sensors utilizing plasmonic stripes of different lengths were numerically simulated, demonstrating bulk refractive index (RI) sensitivities around 5700 nm/RIU for all sensor variants, confirming the theoretical results. The theoretical and numerical results were also validated experimentally through chip-level RI sensing experiments on three fabricated SU-8/Al bimodal sensors with plasmonic sensing lengths of 50, 75, and 100 μm. The obtained experimental RI sensitivities were found to be very close and equal to 4464, 4386, and 4362 nm/RIU, respectively, confirming that the sensing length has no effect on the bimodal sensor sensitivity. The above outcome alleviates the design and optical loss constraints, paving the way for more compact and powerful sensors that can achieve high sensitivity values at ultra-short sensing lengths.

Abstract Cranial cruciate ligament (CCL) rupture is one of the most commonly diagnosed orthopedic conditions of pet dogs, making estimated lifetime cruciate ligament survival an attractive endpoint for studies attempting to define clinical and genetic correlates of rupture risk reduction. Early life experiences contribute significantly to the origins of adult health outcomes, yet our current understanding of modifiable susceptibility factors that drive the high frequency of CCL rupture remains limited. We reasoned that combining lifetime medical history with standardized late-life assessment of lifetime cruciate ligament survival and detailed phenotyping of each dog for selected risk variables would provide a sensitive approach to identify factors that would differentiate between lifelong avoidance versus susceptibility to ligament rupture. Here, we report results of Kaplan–Meier analysis of estimated lifetime cruciate ligament survival and Cox proportional hazards modeling to assess risk variables in a lifetime cohort study of 123 purebred Rottweilers, a breed at high risk for veterinarian-diagnosed CCL rupture. We show that gonad removal during the 24-month developmental period is adversely associated with three measures of susceptibility—increased incidence of CCL rupture, multiplicity (bilateral rupture), and accelerated time to initial CCL failure. Our analysis reveals two other phenotypes—short adult height and the production of offspring (in females)—are associated with significant CCL rupture risk reduction. Together, the results provide clues to an early endocrine influence on lifetime cruciate ligament survival. Further, we identify two distinct clinical syndromes of CCL failure, providing a disease subtyping framework to advance future progress in genetic epidemiology, pathogenesis, and prediction. By conducting an evaluation of estimated lifetime CCL survival in dogs, we show that cruciate ligament survival may be jeopardized by gonad removal during the developmental period. Avoidance of such early environmental adversity may represent an actionable method for the control of canine CCL disease in certain breeds.

Science communication is becoming increasingly important to connect academia and society and to counteract misinformation. Online video platforms, such as YouTube, allow easily accessible communication of scientific knowledge to audiences made up of the general public. In April 2020, a diverse group of researchers from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, launched the YouTube channel called “Wissenschaft fürs Wohnzimmer” (translated to “Living Room Science”) to stream scientific talks about climate change and biodiversity every Thursday evening, with the aim to reach a broad range of members of the public with a general interest in science and climate. Here we report on the numbers and diversity of content, viewers, and presenters from 2 years and 100 episodes of weekly livestreams. Presented topics encompass all areas of polar research, the scientific and societal aspects of climate change and biodiversity loss, and new technologies to deal with the changing world and climate of the future. We show that constant engagement by a group of co-hosts and presenters representing all topics, career stages, and genders enables the continuous growth of views and subscriptions, i.e. a measurable impact. After 783 d, the channel gained 30 251 views and 828 subscribers and hosted well-known scientists, while enabling especially early-career researchers to foster their outreach and media skills. We show that interactive and science-related videos, both live and on-demand, within a pleasant atmosphere, can be produced alongside the main research activity by scientists, while also maintaining high quality. We further discuss the challenges and possible improvements for the future. Our experiences will help other researchers conduct meaningful scientific outreach and push the boundaries of existing formats towards a better understanding of climate change and our planet.

Background: There is wide variation in stress test utilization before major vascular surgery and adherence to practice guidelines is unclear. We defined rates of stress test compliance at our institution and led a quality improvement initiative to improve compliance with American Heart Association (ACC/AHA) guidelines. Methods: We implemented a stress testing order set in the electronic medical record at one tertiary hospital. We reviewed all patients who underwent elective, major vascular surgery in the 6 months before (Jan 1, 2022 – Jul 1, 2022) and 6 months after (Aug 1, 2022 – Jan 31, 2023) implementation. We studied stress test guideline compliance, changes in medical or surgical management, and major adverse cardiac events (MACE). Results: Before order set implementation, 37/122 patients (30%) underwent stress testing within the past year (29 specifically ordered preoperatively) with 66% (19/29) guideline compliance. After order set implementation, 50/173 patients (29%) underwent stress testing within the past year (41 specifically ordered preoperatively) with 80% (33/41) guideline compliance. In the pre- and postimplementation cohorts, stress testing led to a cardiovascular medication change or preoperative coronary revascularization in 24% (7/29) and 27% (11/41) of patients, and a staged surgery or less invasive anesthetic strategy in 14% (4/29) and 4.9% (2/41) of patients, respectively. All unindicated stress tests were surgeon-ordered and none led to a change in management. There was no change in MACE after order set implementation. Conclusions: Electronic medical record-based guidance of perioperative stress testing led to a slight decrease in overall stress testing and an increase in guideline-compliant testing. Our study highlights a need for improved preoperative cardiovascular risk assessment prior to major vascular surgery, which may eliminate unnecessary testing and more effectively guide perioperative decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: For more than a decade, researchers have been gathering evidence suggesting pregnancy may alter the resistance of women to the development of diseases later in life. We wondered if parity—pregnancy resulting in live offspring—could enhance or diminish resistance of bitches to subsequent non-reproductive disease conditions, a hypothesis previously untested in domestic dogs. To pursue this goal, we constructed detailed lifetime reproductive and medical histories from 65 purebred Rottweiler bitches enrolled in an exceptional longevity study. An advantage of studying these bitches was that we could conduct a long-term evaluation of the relationship between parity and the lifelong occurrence of a commonly diagnosed degenerative disease, cranial cruciate ligament (CCL) rupture. Notably, we found parous bitches had a significantly lower likelihood of CCL rupture than nulliparous bitches. This 5.5-fold lower incidence of CCL rupture among parous females could not be explained by differences in diet, physical activity, overweight body condition, or reason for nulliparity. Our work may guide future mechanistic studies on the apparent association between parity and CCL rupture resistance. The research may also stimulate investigations into other non-reproductive health outcomes, such as autoimmune diseases, whose occurrence later in life may be impacted by parity. Emerging evidence in women supports the notion that pregnancy may reset disease resistance, thereby providing protection against subsequent adverse health outcomes, but this hypothesis has not been adequately explored in domestic dogs. Cranial cruciate ligament (CCL) rupture is a degenerative orthopedic disease that frequently affects pet dogs, and its risk has been associated with disruption of the reproductive hormone axis. Our research team is conducting a lifetime cohort study of purebred Rottweilers in North America that have lived 30% longer than breed-average. Detailed medical and reproductive histories of 33 nulliparous and 32 parous Rottweilers were generated from questionnaires and review of medical records. Interviews with owners of bitches in the nulliparous group served to limit selection bias, confirming that in no instance was the reason for nulliparity based upon the owner's suspicion that a bitch had a heightened risk for CCL rupture. The risk of CCL rupture associated with parity and other exposure variables was estimated using multivariate logistic regression. Overall, CCL rupture was diagnosed in 17 of 65 (26%) bitches. Median age at first litter and CCL rupture were 3.6 and 6.5 years, respectively. Compared to nulliparous, parous bitches had a significant 94% reduction in CCL rupture risk adjusted for duration of ovary exposure, overweight body condition, dietary pattern, habitual physical activity, and work/sport activity [ORadjusted (95% CI) = 0.06 (0.01–0.46); (p = 0.006)]. The observed parity-associated CCL rupture risk reduction remained robust in sensitivity analysis excluding six nulliparous bitches for which decision not to breed was based on diagnosis of hip or elbow dysplasia, conditions which may be genetically linked to CCL rupture [ORadjusted (95% CI) = 0.08 (0.01–0.58); (p = 0.01)]. This work sets the stage for replication studies in other canine populations that should begin to explore the mechanistic basis for parity-associated CCL rupture risk reduction and to pursue other non-reproductive health outcomes in bitches whose incidence or severity may be parity-sensitive. [ABSTRACT FROM AUTHOR]

(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (βENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with μCT, sugges-ting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.

Background: The aviation industry is facing a substantial shortage of pilots. Per the International Civil Aviation Organization, it is projected airlines will need 350,000 pilots globally. Aims: Due to the demand of pilots, most of the conversations are focused on quantity rather than quality of the workforce. Educators and researchers in several industries have advocated competency-based education in aviation for decades. Method: Members of the research team documented the consensus decision-making process which determined which competencies would be incorporated into the flight program. Results: Six competencies were selected for the hybrid competency-based education model. Teamwork, decision-making, communication, resilience, leadership, and technical excellence were extensively defined for the aviation program. Discussion/Conclusion: Shifting toward a hybrid competency-based education model is challenging within a large flight program. However, the members of the research team believe the transformation process will improve program outcomes. Next steps include assessment plan development and data collection.

Noble gases are frequently probed for investigating fluid inclusions in minerals to unravel rock-forming processes through time. Over the last decades, heating and crushing have been the two main methods applied for noble gas extraction from fluid inclusions in ultrahigh vacuum (about 10-9 mBar). The heating of minerals or pieces of bulk rock causes the release of noble gases from both fluid inclusions and the mineral or rock matrix, the latter due to temperature-dependent mineral dehydration. Crushing of minerals only affects fluid inclusions and allows a release of noble gases at room temperature with minor contributions from the mineral matrix. This review describes different ultravacuum crushing techniques for noble gas analysis from fluid inclusions. It examines the technical details and operational conditions of each crushing system as well as methods to prepare samples prior to crushing. Crushing systems were found to have unique designs across the different laboratories reviewed; they include single or multiple sample loadings and manual, magnetic, or hydraulic operation of the crushing pistons. Due to the small amounts of noble gases released, the technology requires several mg to a few grams of rock material to achieve a measurement of all stable noble gas isotopes in a single fluid inclusion. While theoretically all stable noble gas isotopes are of interest, the elements and isotopes reported in different studies vary widely and reference materials as well as laboratory intercomparisons are lacking. The review includes applications on the origins of magmatic rocks and geochemical processes in the Earth’s mantle, the origin and chemical composition of deep crustal fluids and how these contribute to the formation of minerals of economic interest, and paleoclimate studies based on speleothems.

Abstract The Mataranka Springs Complex is the headwater of the iconic Roper River of northern Australia. Using environmental tracers measured in springs and nearby boreholes, the origin of groundwater contributing to the springs was evaluated to help assess the impact of proposed groundwater extraction in the Cambrian Limestone Aquifer (CLA) for irrigation agriculture and for hydraulic fracturing in the Beetaloo Sub-basin (an anticipated world-class unconventional gas reserve). Major ions, Sr, 87Sr/86Sr, δ18O-H2O, δ2H-H2O, 3H, 14C-DIC were consistent with regional groundwater from the Daly and Georgina basins of the CLA as the sources of water sustaining the major springs (Rainbow and Bitter) and one of the minor springs (Warloch Pond). However, 3H = 0.34 TU in another minor spring (Fig Tree) indicated an additional contribution from a young (probably local) source. High concentrations of radiogenic 4He (> 10–7 cm3 STP g–1) at Rainbow Spring, Bitter Spring and in nearby groundwater also indicated an input of deeper, older groundwater. The presence of older groundwater within the CLA demonstrates the need for an appropriate baseline characterisation of the vertical exchange of groundwater in Beetaloo Sub-basin ahead of unconventional gas resource development.

Abstract Background The ability of physical therapists (PTs) to accurately identify and reliably measure phoria/tropia is critical in the differential diagnosis of individuals with acute vestibular syndrome and concussion/mild traumatic brain injury. Objectives To determine if PTs may reliably measure phoria and to determine the reliability of two dissociating tests of phoria, the prism neutralized Maddox rod test and modified Thorington method, in normal adults with artificially created phoria. Methods Thirty adults (mean age 24.87 ± 4.74 years) were randomly assigned to wear trial lenses (1, 2, 4, or 6 pd prism left, plain glass right) to create phoria. In sitting and supine, phoria was measured using prism neutralized Maddox rod test and modified Thorington method. Mean, SD, and range of first neutral endpoint were calculated for each examiner. Percentage of trials in agreement (≤ 2 and 4 pd); comparisons within the linear mixed effects regression model; and inter‐rater reliability between examiners was calculated with the intra‐class correlation coefficient (ICC). Results Participants underwent 20 measurements by each examiner. Trial agreement between examiners was 74% (range 13%‐100%) in horizontal and 91% (range 63%‐100%) in vertical plane. Maddox rod test had significantly different means between two examiners (P