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Phenotypic diversity and abundance drive salmon resilience in the face of increasing environmental variability. But what happens when human activities fundamentally alter the habitat complexity that drives this diversity? And how can we restore habitats to recover both diversity and abundance to support salmon persistence in a warming climate? Here, we looked at the impact of a large watershed restoration effort on the abundance and climate resilience of the three remaining core natural spring‐run Chinook Salmon populations in the California Central Valley (Butte, Mill, and Deer Creek). Butte Creek fish, which have floodplain access, had higher overall productivity and faster juvenile growth compared with Mill and Deer Creek populations, and the proportion of floodplain inundation was positively correlated with Butte Creek adult abundance two years later. While Butte Creek exhibited significant increases in abundance post‐restoration (~2000%), it generally exhibited lower phenotypic diversity and only a marginal increase in population stability after restoration based on the coefficient of variation (CV). In particular, Butte Creek salmon tended to exhibit larger drops in escapement following dry years (e.g., return years 2010, 2017) compared with Mill and Deer Creek populations, presumably due to limited inundation of its downstream floodplain. The late‐migrating juvenile strategy (i.e., yearling), which disproportionately supported Mill and Deer Creek populations during droughts, was uncommon among Butte Creek adults (averaging 60% of returns for Mill and Deer Creek vs. 0.3% for Butte Creek). Increased spring‐run stock complex stability was found, post‐restoration, when combining the three spring‐run populations (i.e., lower aggregate CV). However, among‐river pairwise correlations also suggested increased synchronization in population abundances post‐restoration, potentially due to increasing frequency and severity of extreme climatic events (e.g., droughts and ocean warming). This study underscores the importance of restoring a connected mosaic of aquatic habitats across modified landscapes, such as cold water refugia and floodplains, to preserve multiple (across‐population) life history pathways for increasing salmon stock complex stability and abundance. These landscape‐scale process‐based habitat restoration efforts are likely to be crucial for the successful long‐term recovery of vulnerable species in a rapidly changing climate. [ABSTRACT FROM AUTHOR]

Astrocytes are the most abundant glial cell type in the central nervous system and are essential to the development, plasticity, and maintenance of neural circuits. Astrocytes are heterogeneous, with their diversity rooted in developmental programs modulated by the local brain environment. Astrocytes play integral roles in regulating and coordinating neural activity extending far beyond their metabolic support of neurons and other brain cell phenotypes. Both gray and white matter astrocytes occupy critical functional niches capable of modulating brain physiology on time scales slower than synaptic activity but faster than those adaptive responses requiring a structural change or adaptive myelination. Given their many associations and functional roles, it is not surprising that astrocytic dysfunction has been causally implicated in a broad set of neurodegenerative and neuropsychiatric disorders. In this review, we focus on recent discoveries concerning the contributions of astrocytes to the function of neural networks, with a dual focus on the contribution of astrocytes to synaptic development and maturation, and on their role in supporting myelin integrity, and hence conduction and its regulation. We then address the emerging roles of astrocytic dysfunction in disease pathogenesis and on potential strategies for targeting these cells for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Objective: To describe timing, antecedent events, and outcomes in pregnancy‐related stroke (PAS). Methods: Retrospective single‐center cohort of all PAS within 42 days of delivery from September 2010 to May 2021. Data were abstracted from medical records. Results: Among 51 500 births, we identified 91 cases of PAS, with a stroke rate of 177 per 100 000 births. Of all PAS, 62% (n = 56) were hemorrhagic, 56% (n = 51) occurred postpartum, 49% (n = 45) occurred in patients with hypertensive disorders of pregnancy (HDP), and 36% (n = 33) had surgical interventions. There were nine deaths, with a case fatality rate of 9.9%. Of the survivors (n = 82), 37 (45.1%) had residual deficits. Patients with HDP were more likely to have a postpartum stroke than those without HDP (crude relative risk 1.72, 95% confidence interval 1.16–2.55). Among patients with HDP, 89% had at least one severe range blood pressure (BP), with a peak systolic BP of 187.8 ± 27.9 mm Hg and a peak diastolic BP of 109.4 ± 18.4 mm Hg. There was no difference in presenting symptoms (P = 0.120), residual deficits (P = 0.609), or mortality (P = 0.739) between those with or without HDP. Conclusions: At a referral hospital, PAS was uncommon but was associated with a high mortality rate. An improved understanding of the modifiable risk factors is warranted to avert the sequelae of PAS. Synopsis: Pregnancy‐associated strokes are uncommon but associated with a high mortality rate. About half have postpartum presentation, half involve hypertensive disorder, and most present with headaches. [ABSTRACT FROM AUTHOR]

The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs), and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP, and NBN clusters and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands, and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders. Synopsis: Understanding brain development requires detailed insight into the temporal transcription dynamics associated with cell lineage determination. This genome‐wide profiling study provides a comprehensive transcriptomic resource of dorsal cerebral cortical lineages, highlighting the dynamics in gene expression from neural stem cells, basal progenitors, and newborn neurons at the population and single‐cell levels. Neural stem cells (NSCs), basal progenitors (BPs) and newborn neurons (NBN) of the developing cerebral cortex have hallmark gene expression signatures.Dynamics in gene expression define NSC, BP, and NBN heterogeneity, changes in signaling potential, and transcription factor activity.Shifts in transcriptional space over developmental time correspond to neural progenitor fate commitment.Signaling pathways and transcriptional networks during cortical development identify functional nodes and novel gene signatures, implying a 'cellular logic' to fundamental cell fate decisions. [ABSTRACT FROM AUTHOR]

Background: The authors hypothesized that patients developing immune‐related adverse events (irAEs) while receiving immune checkpoint inhibition (ICI) for recurrent/metastatic head and neck cancer (HNC) would have improved oncologic outcomes. Methods: Patients with recurrent/metastatic HNC received ICI at 2 centers. Univariate and multivariate logistic regression, Kaplan‐Meier methods, and Cox proportional hazards regression were used to associate the irAE status with the overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS) in cohort 1 (n = 108). These outcomes were also analyzed in an independent cohort of patients receiving ICI (cohort 2; 47 evaluable for irAEs). Results: The median follow‐up was 8.4 months for patients treated in cohort 1. Sixty irAEs occurred in 49 of 108 patients with 5 grade 3 or higher irAEs (10.2%). ORR was higher for irAE+ patients (30.6%) in comparison with irAE− patients (12.3%; P =.02). The median PFS was 6.9 months for irAE+ patients and 2.1 months for irAE− patients (P =.0004), and the median OS was 12.5 and 6.8 months, respectively (P =.007). Experiencing 1 or more irAEs remained associated with ORR (P =.03), PFS (P =.003), and OS (P =.004) in multivariate analyses. The association between development of irAEs and prolonged OS persisted in a 22‐week landmark analysis (P =.049). The association between development of irAEs and favorable outcomes was verified in cohort 2. ConclusionS: The development of irAEs was strongly associated with an ICI benefit, including overall response, PFS, and OS, in 2 separate cohorts of patients with recurrent/metastatic HNC. In this retrospective analysis of patients with metastatic head and neck cancer receiving immune checkpoint inhibition, the association between the development of immune‐related adverse events and outcomes is investigated. Developing immune‐related adverse events is strongly associated with clinical benefits, including overall response, progression‐free survival, and overall survival, in 2 separate cohorts of patients. [ABSTRACT FROM AUTHOR]

Background: Surgical excision is a mainstay of treatment for non‐melanoma skin cancer (NMSC); improving margin delineation can reduce the need for further monitoring/treatment. The objective of this pilot study was to determine if near‐infrared radiation (NIR) application to skin causes visible changes in normal and NMSC skin, to help delineate margins. Materials/Methods: Eleven biopsy‐proven NMSC lesions were included. The skin was then heated under a 175W NIR heating bulb; margins were traced onto acetate film before and after heating. Lesions were then randomly assigned to excision based on pre‐ or post‐heating margins. Composite images were generated by overlaying the heat and no‐heat lesion contours. All specimens were sent for histopathology. Results: The range of closest margins in the control group was 2.0‐3.0 mm with a median of 2.0 mm; the range in the intervention group was 4.0‐9.0 mm with a median of 5.0 mm. Composite images showed larger heat contours when the initial lesion was larger. There was a statistically significant difference between the two groups. Overall, NIR light caused visible hyperaemia to skin, and more intense erythema to malignant skin lesions. Conclusion: Near‐infrared light may have use in an outpatient setting for skin cancer delineation, possibly reducing the rate of positive margins. [ABSTRACT FROM AUTHOR]

The term "oligometastatic prostate cancer" refers to a heterogeneous group of disease states currently defined solely on the basis of clinical features. Oligorecurrent disease, de novo oligometastases, and oligoprogressive disease likely have unique biologic underpinnings and natural histories. Evidence suggesting the existence of a subset of patients who harbor prostate cancer with limited metastatic potential currently includes disparate and overwhelmingly retrospective reports. Nevertheless, emerging prospective data have corroborated the "better-than-expected," retrospectively observed outcomes, particularly in the setting of oligorecurrent prostate cancer. Improved functional imaging with prostate-specific membrane antigen-targeted strategies may enhance the identification of patients with oligometastatic prostate cancer in the short term. In the long term, refinement of the oligometastatic case definition likely will require biologic risk-stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis-directed therapy, future efforts should focus on conducting high-quality, prospective trials with much-needed molecular correlative studies. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used as tocolytics, which are medications that suppress uterine contractions for preterm birth prevention. Their effect on cerebral/systemic vascular beds poses the question of whether antenatal NSAID exposure is associated with neonatal hypertension. We performed a retrospective case-control study in a tertiary neonatal intensive care unit, including 40 hypertension cases (hospitalized neonates ≥ 35 weeks with systolic BP > 100 mm Hg on three consecutive days) compared to 134 controls matched by gestational age at delivery, plurality, and delivery date. Cases and controls were compared by antenatal NSAID exposure, other common tocolytics, and maternal/neonatal characteristics and complications. Multivariable logistic regression was used to estimate the odds of hypertension among those with prenatal exposure to NSAIDs versus those without exposure. Newborns with hypertension had a lower gestational age at delivery and increased incidence of neonatal complications, including respiratory distress syndrome, bronchopulmonary dysplasia, surfactant administration, longer duration of ventilation, and history of umbilical artery catheterization. Days of indomethacin exposure were positively associated with greater odds of neonatal hypertension (OR 1.17 [1.00 to 1.38], P = 0.055), even after adjustment for other factors associated with neonatal hypertension. Newborns with hypertension were less likely to have been exposed to calcium channel blockers as a tocolytic. The results of our study suggest an association between prenatal exposure to nonsteroidal anti-inflammatory drugs and neonatal hypertension. Furthermore, our data suggest that prenatal calcium channel blocker exposure may protect against the development of neonatal hypertension. Future multicenter studies are needed to understand the risks of tocolytics and subsequent consequences in preterm infants. [ABSTRACT FROM AUTHOR]

The ventral telencephalon is the developmental origin of the basal ganglia and the source of neuronal and glial cells that integrate into developing circuits in other areas of the brain. Radial glia in the embryonic subpallium give rise to an enormous diversity of mature cell types, either directly or through other transit-amplifying progenitors. Here, we review current knowledge about these subpallial neural stem cells and their progeny, focusing on the period of neurogenesis. We describe their cell biological features and the extrinsic and intrinsic molecular codes that guide their fate specification in defined temporal and spatial sequences. We also discuss the role of clonal lineage in the organization and specification of mature neurons. [ABSTRACT FROM AUTHOR]

Although further testing in larger series will potentially verify or refute the concerns raised by Cheung et al, we believe that there is a strong biological rationale as well as sufficient data to support the validity of immune-related adverse events (irAEs) as biomarkers of immunotherapy efficacy as signaled in our retrospective series.1 A few considerations that we would like to highlight include the following: Cheung et al appropriately make a comparison with acneiform rash for epidermal growth factor receptor (EGFR) inhibitors and point out that the early appearance of rash largely abrogates the risk for guarantee-time bias. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. Immune-related adverse events are associated with improved response, progression-free survival, and overall survival for patients with head and neck cancer receiving immune checkpoint inhibitors. [Extracted from the article]

Adenylate cyclase toxin domain (CyaA-ACD) is a calmodulin (CaM)-dependent adenylate cyclase involved in Bordetella pertussis pathogenesis. Calcium (Ca2+) and magnesium (Mg2+) concentrations impact CaM-dependent CyaA-ACD activation, but the structural mechanisms remain unclear. In this study, NMR, dynamic light scattering, and native PAGE were used to probe Mg2+-induced transitions in CaM's conformation in the presence of CyaA-ACD. Mg2+ binding was localized to sites I and II, while sites III and IV remained Ca2+ loaded when CaM was bound to CyaA-ACD. 2Mg2+/2Ca2+-loaded CaM/CyaA-ACD was elongated, whereas mutation of site I altered global complex conformation. These data suggest that CyaA-ACD interaction moderates CaM's Ca2+- and Mg2+-binding capabilities, which may contribute to pathobiology. [ABSTRACT FROM AUTHOR]

Research summary: How do external venturing units effectively achieve external knowledge search and integration of their initiatives with mainstream organizational units?We investigate this largely unexplored question through an inductive study of 17 corporate venture capital units. We document a set of five novel practices that influence the efficacy of a unit's external search and internal integration and identify how these practices complement a broader set of practices used by all units. We highlight the entrepreneurial nature of managing an external venturing unit, often to overcome unfavorable corporate contexts, a perspective that prior research has largely overlooked. Our findings provide unique insights into why some corporate investors are better at learning from external start-ups than others. Managerial summary: External venturing involves strategic partnerships by established firms with entrepreneurial ventures. Top management usually tasks autonomous units with searching for willing and potentially valuable partners. These units must integrate their activities with the operations of parent firms to elicit cooperation from important business units. To understand how external venturing units implement search and integration in combination, we study corporate venture capital (CVC) units, which form external partnerships through minority investments in start-ups. While all units adopted fundamental processes that are well established in the venture capital community, certain processes that are idiosyncratic to corporate investing helped units demonstrate superior performance in their strategic missions. These processes often required CVC unit managers to be entrepreneurial and politically savvy in building connections with relevant personnel in parent firms. [ABSTRACT FROM AUTHOR]

Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent. [ABSTRACT FROM AUTHOR]

While it is widely recognized that financial stock portfolios can be stabilized through diverse investments, it is also possible that certain habitats can function as natural portfolios that stabilize ecosystem processes. Here we propose and examine the hypothesis that free-flowing river networks act as such portfolios and confer stability through their integration of upstream geological, hydrological, and biological diversity. We compiled a spatially (142 sites) and temporally (1980-present) extensive data set on fisheries, water flows, and temperatures, from sites within one of the largest watersheds in the world that remains without dams on its mainstem, the Fraser River, British Columbia, Canada. We found that larger catchments had more stable fisheries catches, water flows, and water temperatures than smaller catchments. These data provide evidence that free-flowing river networks function as hierarchically nested portfolios with stability as an emergent property. Thus, free-flowing river networks can represent a natural system for buffering variation and extreme events. [ABSTRACT FROM AUTHOR]

Increases in crop yields and changing cropping patterns have placed stress on agribusiness handling and storage facilities. The objective of this research is to gain insight into the relationship between safety culture and safety performance, and to identify the determinants of safety culture in agribusinesses. The research suggests that investments in labor inputs such as increased training, consistent discipline, and recognition of safety achievements all increase safety culture. Furthermore, improvements in employee perceptions of safety culture have a positive impact on reducing employee injuries. Congress has recently funded nine centers to work on occupational health and safety research in agriculture, fisheries, and forestry. [ABSTRACT FROM AUTHOR]

ABSTRACT The objective of this research is to identify determinants that influence sugar beet plant survival. Important determinants identified from the literature are hypothesized to include capacity, market concentration, ownership, government policies, and historical industry events unique to this industry. As suggested by industrial organization theory, plants with greater capacity and multi-plant firms have lower rates of closure. Likewise, the use of a high tariff on imports of refined sugar, the use of quotas on imports of sugar from various countries, and a price support program that encouraged plants to become more cost efficient have lessened the rates of closure. [ABSTRACT FROM AUTHOR]

Mortalin, a member of the Hsp70-family of molecular chaperones, functions in a variety of processes including mitochondrial protein import and quality control, Fe-S cluster protein biogenesis, mitochondrial homeostasis, and regulation of p53. Mortalin is implicated in regulation of apoptosis, cell stress response, neurodegeneration, and cancer and is a target of the antitumor compound MKT-077. Like other Hsp70-family members, Mortalin consists of a nucleotide-binding domain (NBD) and a substrate-binding domain. We determined the crystal structure of the NBD of human Mortalin at 2.8 Å resolution. Although the Mortalin nucleotide-binding pocket is highly conserved relative to other Hsp70 family members, we find that its nucleotide affinity is weaker than that of Hsc70. A Parkinson's disease-associated mutation is located on the Mortalin-NBD surface and may contribute to Mortalin aggregation. We present structure-based models for how the Mortalin-NBD may interact with the nucleotide exchange factor GrpEL1, with p53, and with MKT-077. Our structure may contribute to the understanding of disease-associated Mortalin mutations and to improved Mortalin-targeting antitumor compounds. [ABSTRACT FROM AUTHOR]

R4986 --> 811.3 --> Abdominal pain is a major symptom of diseases associated with microbial dysbiosis. Disruption of the gut microbiota with antibiotics increases visceral pain, and germ‐free mice are more prone to pain than conventionally‐raised mice. However, the mechanisms underlying microbial modulation of pain remain elusive. We hypothesized that disruption of the intestinal microbiota modulates the excitability of peripheral nociceptive neurons. Patch clamp electrophysiological recordings of dorsal root ganglion (DRG) neuron excitability were obtained from control mice and mice treated with the non‐absorbable antibiotic vancomycin (50 µg/ml in drinking water) for one week. Ten days prior to recording visceromotor response (VMR) telemetric transmitters were placed into the abdominal cavity of the mice and allowed to recover. VMR was measured by insertion of balloon catheter into the rectum under light anesthetization in both control and vancomycin treated mice, then distended to 80 mmHg and VMR recorded. Bacterial dysbiosis was verified by metagenomic analysis of stool microbial composition. Mice treated with vancomycin were more sensitive to colorectal distension in vivo (VMR increased by 70% at 80 mmHg compared to control), and DRG neurons from vancomycin‐treated mice were hyperexcitable in vitro compared to water‐treated controls (rheobase decreased by 30% relative to control). Interestingly, hyperexcitability of DRG neurons was not restricted to gut projecting neurons, suggesting a widespread effect of gut dysbiosis on pain pathways. Incubation of DRG neurons from naïve mice in serum from vancomycin‐treated mice increased neuron excitability (rheobase decreased by 30% relative to control), suggesting that microbial dysbiosis alters circulating mediators that influence nociception. Multiplex ELISA measurements did not detect any significant changes in serum cytokines or chemokines between vancomycin‐treated and control mice. The cysteine protease inhibitor E64 (30 nM) and the protease‐activated receptor 2 (PAR2) antagonist GB‐83 (10 µM) each blocked the increase in DRG neuron excitability in response to serum from vancomycin‐treated mice. Naïve DRG neurons incubated with fecal supernatants from vancomycin‐treated mice also exhibited increased excitability (rheobase decreased by 40% relative to control), but supernatants derived from colonic tissue failed to cause hyperexcitability. Overall, this data suggests that microbial dysbiosis within the gut alters pain sensitivity. This effect is not caused by inflammation or host derived factors, rather bacterially‐derived cysteine proteases activating PAR2 on DRG neurons. [ABSTRACT FROM AUTHOR]

Conservation successes can and do happen, however, the process by which society achieves them remains unclear. Using a novel culturomics approach, we analyse word usage within digitized texts to assess the chronological order in which scientists, the public, and policymakers engage in the conservation process for three prominent conservation issues: acid rain in North America, global DDT contamination, and the overexploitation of African elephants for ivory. Variation in the order and magnitude of sector responses among the three issues emphasizes that there are multiple pathways to conservation success and that science is just one component. Our study highlights that while scientists can initiate the process, policy change does not occur in the absence of public interest. We suggest that the fate of conservation action is not solely determined by the scientific soundness of the conservation plan, but rather requires the engagement of scientists, public, and policy makers alike. [ABSTRACT FROM AUTHOR]

The process of learning new surgical technical skills is vital to the career of a surgeon. The acquisition of these new skills is influenced greatly by visual-spatial ability (VSA) and may be difficult for some learners to rapidly assimilate. In many cases, the role of VSA on the acquisition of a novel technical skill has been explored; however, none have probed the impact of a three-dimensional (3D) video learning module on the acquisition of new surgical skills. The first aim of this study is to capture spatially complex surgical translational flaps using 3D videography and incorporate the footage into a self-contained e-learning module designed in line with the principles of cognitive load theory. The second aim is to assess the efficacy of 3D video as a medium to support the acquisition of complex surgical skills in novice surgeons as evaluated using a global ratings scale. It is hypothesized that the addition of depth in 3D viewing will augment the learner's innate visual spatial abilities, thereby enhancing skill acquisition compared to two-dimensional viewing of the same procedure. Despite growing literature suggesting that 3D correlates directly to enhanced skill acquisition, this study did not differentiate significant results contributing to increased surgical performance. This topic will continue to be explored using more sensitive scales of measurement and more complex 'open procedures' capitalizing on the importance of depth perception in surgical manipulation. Anat Sci Educ. © 2012 American Association of Anatomists. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine the efficacy of interventions to improve and monitor skin scarring, a valid assessment instrument must be used. Current tools used for the evaluation of skin scarring employ equal appearing interval (EAI) scales that assume scar dimensions conform to linear models. Some scar features meet these assumptions, whereas others may not be accurately described. This study determined if current methods of scar evaluation validly characterize inherent features of scars, and in doing so, empirically validate if specific scar dimensions were best represented by linear or nonlinear mathematical models. Study Design: Prospective, randomized, cross-over trial. Methods: Twenty-seven observers evaluated 30 scar photos utilizing both EAI and direct magnitude estimation (DME) scaling methods. The method of scaling and the assessed dimensions of vascularity, pigmentation, thickness, pliability, and surface area were randomized. EAI and DME data were evaluated to identify whether each scar dimension conformed to linear or curvilinear mathematical models. Results: Best-fit analysis revealed the dimensions of vascularity and pigmentation to be more accurately described using curvilinear functions, whereas pliability, thickness and surface area were best defined using linear models. Conclusions: The scar dimension under assessment must be considered when attempting to validly apply an assessment instrument. Several commonly evaluated dimensions of skin scarring are not appropriately characterized using linear EAI scales. Thus, present assessment instruments must be revised to account for this aberration to allow for a valid means of objectively evaluating skin scarring. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

Objective: This study assessed the utility of focused scar injury with an ink-free tattooing technique combined with UV light exposure for the treatment of hypopigmented cervicofacial scars. Study Design: Pilot prospective, randomized, control trial. Subjects: Individuals with long-standing hypopigmented cervicofacial scars. Methods: Twenty individuals randomly underwent UVA light exposure with or without dry tattooing. Scars were evaluated pretreatment and at seven-months post-treatment. Outcome measures included observer and patient subjective assessment of the scar, and objective evaluation of the erythema and melanin content of the scar and the surrounding skin. Results: The tattoo group demonstrated statistically significant improvement in the subjective evaluation of their scars. Scar melanin content reached equivalence with the surrounding skin. Observer and patient subjective global ratings support the use of dry tattooing. Conclusions: Dry-tattooing followed by UV light exposure may provide a safe and effective means for the treatment of hypopigmented scars. [Copyright &y& Elsevier]

Objective: This study assessed rhinometric improvement in nasal airflow, perceived comfort, and the utility of nasal dilation devices for individuals with nasal obstruction treated with an external nasal dilator (END) or a novel internal nasal dilation stent (INDS). Study Design: Prospective, randomized, crossover trial. Subjects: Individuals with symptoms of nasal obstruction. Methods: Twenty-three participants underwent rhinometry and a trial with a novel INDS and a validated END. Devices were used in a randomized, crossover fashion. Nasal airflow, maximum use, continuous use, comfort, and challenge with these devices were assessed. Results: The END and INDS showed greater nasal airflow from baseline, with the INDS being significantly better than the END. The INDS was used significantly more than the END, and demonstrated significantly greater comfort and less associated challenge. Conclusions: The novel INDS showed 3.4 times improved nasal airflow from baseline, was used maximally and continuously longer than a validated END, and was judged to be significantly more tolerable. [Copyright &y& Elsevier]

Objective: To evaluate changes in dermal characteristics with subdermal fat grafting of cutaneous scars. Design: Prospective cohort. Methods: Fourteen patients with various scar types were treated with subdermal fat grafting over 30 months. Dermal elasticity, vascularity, pigmentation, patient perception and satisfaction, and observer assessment of scar characteristics were evaluated preoperatively and 1 year after treatment with validated objective and subjective measures. Results: Significant improvements were observed in dermal elasticity, patient and observer perception of scar thickness, patient perception of stiffness, and observer perception of relief and pliability (P < 0.05). A trend toward significance was seen in observer assessment of height as evaluated by the Vancouver Scar Scale (P < 0.1). No significant differences were seen in quantitatively and qualitatively measured vascularity and pigmentation (P > 0.1). No significant difference in pain, pruritis, and irregularity were reported (P > 0.1). Conclusion: Although fat grafting represents a subdermal process, it appears to improve certain quantitative and qualitative dermal characteristics. Fat grafting does not appear to affect skin color, vascularity, or patient symptoms. [Copyright &y& Elsevier]

Objective: It is proposed to test the practicality of septopalatal protraction in the unilateral cleft palate infant for purposes of straightening the nasal septum and thus relieving nasal airflow obstruction and its detrimental sequelae. Methods: Alternate infants affected with complete unilateral palatal clefts had septopalatal protraction for a period of 6 to 8 weeks (protraction group; n = 4). Septal deviation was measured by a standardized technique that used computed tomography scans. The remaining infants had no protraction and served as controls (nonprotraction group; n = 5). Septal deviation was measured in the nonprotraction group from palatoseptal dental molds. Results: A total of 9 patients were studied. All patients in the nonprotraction group had worsening of nasal septal deviation over a period of 8 weeks compared with the protraction group, which had complete nasal septal straightening. Differences in septal angle deviation between the protraction group and nonprotraction group at the end of the study were statistically significant (P ≤ 0.01) as measured by the paired Student t test. Conclusions: Septopalatal protraction in the newborn appears to provide a means for correcting nasal septal deviation in complete unilateral cleft palate infants. Septopalatal protraction in the newborn is relatively easy and safe. EBM rating: B-2 [Copyright &y& Elsevier]

Anxiety disorders are the most common mental illnesses - afflicting 19% of Americans every year and 31% within their lifetimes - yet diagnoses remain based on symptom checklists because existing technologies have yet to produce biomarkers sufficiently robust for clinical use. Some techniques provide superior spatial resolution of deep brain regions implicated in anxiety but have poor time resolution; while others measure signals in real time but lack spatial resolution. Often, the goal of probing deep brain regions in humans for anxiety research is to measure a putative analogue of a mammalian brain rhythm linked to behaviour that is suggestive of anxiety. This 4-12 Hz, 1-2 mV, behaviourally modulated, nearly sinusoidal "hippocampal theta rhythm" (hTheta) is one of the largest normal extracellular synchronous signals in mammals and although it has been linked to anxiety processes, its function remains unclear. This paper reviews the literature on hTheta as it relates to anxiety and sensory, in particular vestibuloacoustic, signals, concludes that hTheta can modulate sensory signals during anxiety and posits that such modulation of vestibular signals may be an anxiety biomarker that could be detected non-invasively in humans., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

This study examines links between self-disclosure and relationship quality with close friends from adolescence to adulthood. A diverse community sample of adolescents (N = 184) participated in survey and observational measures annually from ages 13 through 29, along with their close friends and romantic partners. Random intercept cross-lagged panel modeling (RICLPM) was used to parse markers of within-individual change from age 13 to 18. Long-term longitudinal path models also investigated cascading associations among self-disclosure and relationship quality, on aggregate, from adolescence to adulthood. Adolescents who reported a higher-quality friendship in a given year demonstrated greater-than-expected increases in self-disclosure the following year, and an adolescent demonstrated high self-disclosure one year reported greater-than-expected increases in friendship quality the following year. Higher mean self-disclosure in adolescence predicted higher mean self-disclosure in adulthood. Results are interpreted as identifying high-quality adolescent friendships as key contexts for developing intimacy-building capacities (i.e. self-disclosure), which sets the stage for satisfying close relationships in adulthood., (© 2024 The Authors. Journal of Research on Adolescence published by Wiley Periodicals LLC on behalf of Society for Research on Adolescence.)

Evidence from medicine and other fields has shown that gender diversity results in better decision making and outcomes. The incoming workforce of congenital heart specialists (especially in pediatric cardiology) appears to be more gender balanced, but past studies have shown many inequities. Gender-associated differences in leadership positions, opportunities presented for academic advancement, and recognition for academic contributions to the field persist. In addition, compensation packages remain disparate if evaluated based on gender with equivalent experience and expertise. This review explores these inequities and has suggested individual and institutional changes that could be made to recruit and retain women, monitor the climate of the institution, and identify and eliminate bias in areas like salary and promotions.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease, characterised by pruritus and increased total serum bile acids (TSBA), Australian incidence 0.6-0.7%. ICP is diagnosed by non-fasting TSBA ≥19 μmol/L in a pregnant woman with pruritus without rash without a known pre-existing liver disorder. Peak TSBA ≥40 and ≥100 μmol/L identify severe and very severe disease respectively, associated with spontaneous preterm birth when severe, and with stillbirth, when very severe. Benefit-vs-risk for iatrogenic preterm birth in ICP remains uncertain. Ursodeoxycholic acid remains the best pharmacotherapy preterm, improving perinatal outcome and reducing pruritus, although it has not been shown to reduce stillbirth., (© 2023 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

This study examined development of emotional support competence within close friendships across adolescence. A sample of 184 adolescents (53% girls, 47% boys; 58% White, 29% Black, 14% other identity groups) participated in seven waves of multimethod assessments with their best friends and romantic partners from age 13 to 24. Latent change score models identified coupled predictions over time from emotional support competence to increasing friendship quality and decreasing support received from friends. Friend-rated emotional support competence in adolescence predicted supportiveness in adult romantic relationships, over and above supportiveness in adolescent romantic relationships. Teen friendships may set the stage for developing emotional support capacities that progress across time and relationships into adulthood., (© 2022 The Authors. Journal of Research on Adolescence published by Wiley Periodicals LLC on behalf of Society for Research on Adolescence.)

Background Ectonucleotidases maintain vascular homeostasis by metabolizing extracellular nucleotides, modulating inflammation and thrombosis, and potentially, myocardial flow through adenosine generation. Evidence implicates dysfunction or deficiency of ectonucleotidases CD39 or CD73 in human disease; the utility of measuring levels of circulating ectonucleotidases as plasma biomarkers of coronary artery dysfunction or disease has not been previously reported. Methods and Results A total of 529 individuals undergoing clinically indicated positron emission tomography stress testing between 2015 and 2019 were enrolled in this single-center retrospective analysis. Baseline demographics, clinical data, nuclear stress test, and coronary artery calcium score variables were collected, as well as a blood sample. CD39 and CD73 levels were assessed as binary (detectable, undetectable) or continuous variables using ELISAs. Plasma CD39 was detectable in 24% of White and 8% of Black study participants ( P =0.02). Of the clinical history variables examined, ectonucleotidase levels were most strongly associated with underlying liver disease and not other traditional coronary artery disease risk factors. Intriguingly, detection of circulating ectonucleotidase was inversely associated with stress myocardial blood flow (2.3±0.8 mL/min per g versus 2.7 mL/min per g±1.1 for detectable versus undetectable CD39 levels, P <0.001) and global myocardial flow reserve (Pearson correlation between myocardial flow reserve and log(CD73) -0.19, P <0.001). A subanalysis showed these differences held true independent of liver disease. Conclusions Vasodilatory adenosine is the expected product of local ectonucleotidase activity, yet these data support an inverse relationship between plasma ectonucleotidases, stress myocardial blood flow (CD39), and myocardial flow reserve (CD73). These findings support the conclusion that plasma levels of ectonucleotidases, which may be shed from the endothelial surface, contribute to reduced stress myocardial blood flow and myocardial flow reserve.

Background: Two-dimensional (2D) strain imaging has become an important tool in assessing subclinical myocardial dysfunction in children. However, there are no published normal values for vendor-independent strain software. The aim of this study was to estimate 2D strain values in a cohort of healthy children using Tomtec cardiac performance analysis (CPA), a vendor-independent software., Methods: Transthoracic echocardiograms of healthy pediatric outpatients (0-18 years) were retrospectively analyzed from the Vanderbilt Pediatric Heart Institute using CPA. The cardiac assessment included global longitudinal strain (GLS), global longitudinal strain rate (GLSR), global circumferential strain (GCS), and global circumferential strain rate (GCSR). Mean strain values with standard deviation (SD) are reported. The Wilcoxon rank sum test, linear regression, and one-way analysis of variance were used to assess differences among the various groups., Results: Among 142 children analyzed, 79 (56%) were male, and the median age was 5.5 (range, 0-18) years. The mean (SD) strain values were GLS -19.3 ± 3.4, GLSR -1.1 ± .22; GCS -24.7 ± 4.3, GCSR -1.5 ± .28. Age accounted for <8% of the variation in GLS, GCS, and GCSR. However, for GLSR, there was a statistically significant difference between younger and older age groups with higher GLSR in the younger age group. Age accounted for ∼25% of the variation in GLSR (R 2  = .25, p < 0.001). There were no significant differences in strain based on sex., Conclusion: We report normal myocardial strain values in healthy children by age for strain using CPA. These values add to the growing body of literature on myocardial strain in children and provide necessary data for the interpretation of strain imaging., (© 2022 Wiley Periodicals LLC.)

The efficacy of COVID-19 convalescent plasma (CCP) as a treatment for hospitalized patients with COVID-19 remains somewhat controversial; however, many studies have not evaluated CCP documented to have high neutralizing antibody titer by a highly accurate assay. To evaluate the correlation of the administration of CCP with titer determined by a live viral neutralization assay with 7- and 28-day death rates during hospitalization, a total of 23 118 patients receiving a single unit of CCP were stratified into two groups: those receiving high titer CCP (>250 50% inhibitory dilution, ID50; n = 13 636) or low titer CCP (≤250 ID50; n = 9482). Multivariable Cox regression was performed to assess risk factors. Non-intubated patients who were transfused with high titer CCP showed 1.1% and 1.7% absolute reductions in overall 7- and 28-day death rates, respectively, compared to those non-intubated patients receiving low titer CCP. No benefit of CCP was observed in intubated patients. The relative benefit of high titer CCP was confirmed in multivariable Cox regression. Administration of CCP with high titer antibody content determined by live viral neutralization assay to non-intubated patients is associated with modest clinical efficacy. Although shown to be only of modest clinical benefit, CCP may play a role in the future should viral variants develop that are not neutralized by other available therapeutics., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background The effectiveness of a nurse-led in-hospital monitoring protocol with mobile ECG (iECG) was investigated for detecting atrial fibrillation in patients post-ischemic stroke or post-transient ischemic attack. The study aimed to assess the cost-effectiveness of using iECG during the initial hospital stay compared with standard 24-hour Holter monitoring. Methods and Results A Markov microsimulation model was constructed to simulate the lifetime health outcomes and costs. The rate of atrial fibrillation detection in iECG and Holter monitoring during the in-hospital phase and characteristics of modeled population (ie, age, sex, CHA2DS2-VASc) were informed by patient-level data. Costs related to recurrent stroke, stroke management, medications (new oral anticoagulants), and rehabilitation were included. The cost-effectiveness analysis outcome was calculated as an incremental cost per quality-adjusted life-year gained. As results, monitoring patients with iECG post-stroke during the index hospitalization was associated with marginally higher costs (A$31 196) and greater benefits (6.70 quality-adjusted life-years) compared with 24-hour Holter surveillance (A$31 095 and 6.66 quality-adjusted life-years) over a 20-year time horizon, with an incremental cost-effectiveness ratio of $3013/ quality-adjusted life-years. Monitoring patients with iECG also contributed to lower recurrence of stroke and stroke-related deaths (140 recurrent strokes and 20 deaths avoided per 10 000 patients). The probabilistic sensitivity analyses suggested iECG is highly likely to be a cost-effective intervention (100% probability). Conclusions A nurse-led iECG monitoring protocol during the acute hospital stay was found to improve the rate of atrial fibrillation detection and contributed to slightly increased costs and improved health outcomes. Using iECG to monitor patients post-stroke during initial hospitalization is recommended to complement routine care.

Obesity has been associated with increased incidence of comorbidities and shorter life expectancy, and it has generally been assumed that patients with obesity should have inferior outcomes after surgery. Previous literature has often demonstrated equivalent or even improved rates of mortality after cardiac surgery when compared to their lower-weight counterparts, coined the obesity paradox. Herein, we aim to review the literature investigating the impact of obesity on surgical valve interventions. PubMed and Embase were systematically searched for articles published from 1 January 2000 to 15 October 2021. A total of 1315 articles comparing differences in outcomes between patients of varying body mass index (BMI) undergoing valve interventions were reviewed and 25 were included in this study. Patients with higher BMI demonstrated equivalent or reduced rates of postoperative myocardial infarction, stroke, reoperation rates, acute kidney injury, dialysis and bleeding. Two studies identified increased rates of deep sternal wound infection in patients with higher BMI, although the majority of studies found no significant difference in deep sternal wound infection rates. The obesity paradox has described counterintuitive outcomes predominantly in coronary artery bypass grafting and transcatheter aortic valve replacement. Recent literature has identified similar trends in other heart valve interventions. While the obesity paradox has been well characterized, its causes are yet to be identified. Further study is essential in order to identify the causes of the obesity paradox so patients of all body sizes can receive optimal care., (© 2021 World Obesity Federation.)

Visual analysis is the primary method used to interpret single-case experimental design (SCED) data in applied behavior analysis. Research shows that agreement between visual analysts can be suboptimal at times. To address the inconsistent interpretations of SCED data, recent structured visual-analysis technological advancements have been developed. To assess the extent to which structured visual analysis is used to guide or supplement applied behavior analysts' interpretation of SCED graphs, a systematic review between the years of 2015 to 2020 in the Journal of Applied Behavior Analysis was conducted. Findings showed that despite recent efforts to develop structured visual-analysis tools and criteria, these methods are rarely used to analyze SCED data. An overview of structured visual-analysis tools is shared, their utility is delineated, common characteristics are brought to light, and future directions for both research and their clinical use are highlighted., (© 2022 Society for the Experimental Analysis of Behavior (SEAB).)

Background Objective markers of cardiac function are limited in the outpatient setting and may be beneficial for monitoring patients with chronic cardiac conditions. We assess the accuracy of a scale, with the ability to capture ballistocardiography, electrocardiography, and impedance plethysmography signals from a patient's feet while standing on the scale, in measuring stroke volume and cardiac output compared with the gold-standard direct Fick method. Methods and Results Thirty-two patients with unexplained dyspnea undergoing level 3 invasive cardiopulmonary exercise test at a tertiary medical center were included in the final analysis. We obtained scale and direct Fick measurements of stroke volume and cardiac output before and immediately after invasive cardiopulmonary exercise test. Stroke volume and cardiac output from a cardiac scale and the direct Fick method correlated with r =0.81 and r =0.85, respectively ( P <0.001 each). The mean absolute error of the scale estimated stroke volume was -1.58 mL, with a 95% limits of agreement of -21.97 to 18.81 mL. The mean error for the scale estimated cardiac output was -0.31 L/min, with a 95% limits of agreement of -2.62 to 2.00 L/min. The changes in stroke volume and cardiac output before and after exercise were 78.9% and 96.7% concordant, respectively, between the 2 measuring methods. Conclusions In a proof-of-concept study, this novel scale with cardiac monitoring abilities may allow for noninvasive, longitudinal measures of cardiac function. Using the widely accepted form factor of a bathroom scale, this method of monitoring can be easily integrated into a patient's lifestyle.

Objectives: Current methods of quantifying defects of dental enamel (DDE) include either gross or low-level examination for linear enamel hypoplasia, histological analysis of striae of Retzius, or scanning electron microscopy (SEM) of a tooth or a tooth cast. Gross examination has been shown to miss many defects. Other methods can be destructive, require transporting samples, and are expensive. Here, we show that digital light microscopy (DLM) can be used for the analysis of DDE as indicated by widened perikymata spacing (WPS). This method takes advantage of high-power (100×) microscopy, but is non-destructive, can be implemented almost anywhere, and is inexpensive., Materials and Methods: As proof of concept, we created photomontages of labial surfaces of five human canines from images made using DLM and SEM. We counted and measured the widths of all visible perikymata for each imaging modality and fit measurements to a negative curve representing the expected values for each tooth. We calculated residuals for each measurement. WPS were defined when R 2 was in the 90th percentile, and were considered matched in DLM and SEM images when observed within the same decile of the tooth surface., Results: There were more WPS detected in the images derived from DLM than from SEM. Overall, the data derived from the two imaging modalities provided similar information about the frequency and timing of stress during dental development., Conclusions: The method described here allows for DDE data acquisition as WPS from large samples, making feasible population-level studies that reflect sophisticated understanding of dental development., (© 2021 Wiley Periodicals LLC.)

For more than four decades, researchers have used meta-analyses to synthesize data from multiple experimental studies often to draw conclusions that are not supported by individual studies. More recently, single-case experimental design (SCED) researchers have adopted meta-analysis techniques to answer research questions with data gleaned from SCED experiments. Meta-analyses enable researchers to answer questions regarding intervention efficacy, generality, and condition boundaries. Here we discuss meta-analysis techniques, the rationale for their adaptation with SCED studies, and current indices used to quantify the effect of SCED data in applied behavior analysis., (© 2021 Society for the Experimental Analysis of Behavior (SEAB).)

Post-pericardiotomy syndrome (PPS) is a common inflammatory process following cardiac surgery, in which the pericardial space was opened. Pericardial effusion (PE) is a common manifestation in PPS; however, coronary artery dilation is not associated with PPS. Inflammatory vasculitis in children are known to cause coronary dilation, in conditions such as in Kawasaki Disease (KD). We report a patient with PPS and concomitant coronary dilation by transthoracic echocardiography (TTE) following repair of her ventricular septal defect (VSD)., (© 2021 Wiley Periodicals LLC.)

Objective: The goal of this manuscript was to report the clinical outcomes of the initial series of 100 consecutive Right Anterior Mini Thoracotomy (RAMT) aortic valve replacement (AVR) implantations at a Canadian Center., Methods: This retrospective study reported the clinical outcomes of the first 100 patients who underwent the RAMT approach for isolated surgical AVR in Calgary, Canada, between 2016 and 2020. Primary outcomes were death within 30 days of surgery and disabling stroke. Secondary outcomes included surgical times, the need for permanent pacemaker (PPM), incidence of postoperative blood transfusion in the intensive care unit (ICU), postsurgical atrial fibrillation (AF), length of ICU/hospital stay, postsurgical AF, residual paravalvular leak (PVL), postoperative transvalvular gradient, need for postsurgical intravenous opioids, duration of invasive ventilation in the ICU, and chest tube output in the first 12 h postsurgery., Results: In this study, 54 patients were male, and the average age of the cohort was 72 years. Mortality within 30 days of surgery was 1% with no disabling postoperative strokes. Mean cardiopulmonary bypass and cross clamp was 84 and 55 min, respectively. PPM rate was 3%, incidence of blood transfusion in the ICU was 4%, and the rate of postoperative AF was 23%. Median length of ICU and hospital stay was 1 and 5 days, respectively. Rate of mild or greater residual PVL was 3%, while the average residual transvalvular mean gradient was 8.5 mmHg., Conclusion: The sternum-sparing RAMT approach can be safely integrated into surgical practice as a minimally invasive alternative for isolated AVR, and can reduce postoperative bleeding and narcotic requirements., (© 2021 Wiley Periodicals LLC.)