Restoring thalamocortical circuit dysfunction by correcting HCN channelopathy in Shank3 mutant mice.

Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3 mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.

Real-world use of long-acting cabotegravir and rilpivirine: 12-month results of the inJectable Antiretroviral therapy feasiBility Study (JABS).

OBJECTIVES: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long-acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non-adherence. METHODS: JABS was a 12-month, single-centre, single-arm, open-label phase IV study of long-acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV-1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14-day dosing window over 12 months, out of the total prescribed doses. Secondary endpoints included proportions of missed appointments, use of oral bridging, discontinuations, virological failures, adverse events and participant-reported outcomes. A multidisciplinary adherence programme embedded in the clinical service known as REACH provided support to JABS participants. RESULTS: Of 60 participants enrolled by May 2022, 60% had one or more complexity or vulnerability factors identified, including absence of social supports (50%), mental health issues, alcohol or drug use (30%) and financial hardship or instability (13%), among others. Twenty-seven per cent of participants had historical non-adherence to antiretroviral therapy. Out of 395 prescribed doses, 97.2% of injections were administered within correct dosing windows at clinic visits. Two courses of short-term oral bridging were required. The rate of injection site reactions was 29%, the majority being grade 1-2. There were no virological failures, no serious adverse events and only one injection-related study discontinuation. High baseline treatment satisfaction and acceptability of injections increased by month 12. Those with vulnerability factors had similar adherence to injections as those without such factors. Ninety-eight per cent of the participants who completed 12 months on the study have maintained long-acting therapy, virological suppression and retention in care. CONCLUSIONS: Long-acting cabotegravir plus rilpivirine was associated with very high adherence, maintenance of virological suppression, safety and treatment satisfaction in a diverse Australian clinic population, comparable to results of phase III randomized clinical trials. Individuals with vulnerability factors can achieve adherence to injections with individualized support. Long-acting therapies in this group can increase the subsequent engagement in clinical care.

Enhancement of mediodorsal thalamus rescues aberrant belief dynamics in a mouse model with schizophrenia-associated mutation.

Optimizing behavioral strategy requires belief updating based on new evidence, a process that engages higher cognition. In schizophrenia, aberrant belief dynamics may lead to psychosis, but the mechanisms underlying this process are unknown, in part, due to lack of appropriate animal models and behavior readouts. Here, we address this challenge by taking two synergistic approaches. First, we generate a mouse model bearing patient-derived point mutation in Grin2a (Grin2aY700X+/-), a gene that confers high-risk for schizophrenia and recently identified by large-scale exome sequencing. Second, we develop a computationally trackable foraging task, in which mice form and update belief-driven strategies in a dynamic environment. We found that Grin2aY700X+/- mice perform less optimally than their wild-type (WT) littermates, showing unstable behavioral states and a slower belief update rate. Using functional ultrasound imaging, we identified the mediodorsal (MD) thalamus as hypofunctional in Grin2aY700X+/- mice, and in vivo task recordings showed that MD neurons encoded dynamic values and behavioral states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/- mice, and enhancing MD activity rescued task deficits in Grin2aY700X+/- mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction, and a potential target for future therapeutics.

CB1R dysfunction of inhibitory synapses in the ACC drives chronic social isolation stress-induced social impairments in male mice.

Social isolation is a risk factor for multiple mood disorders. Specifically, social isolation can remodel the brain, causing behavioral abnormalities, including sociability impairments. Here, we investigated social behavior impairment in mice following chronic social isolation stress (CSIS) and conducted a screening of susceptible brain regions using functional readouts. CSIS enhanced synaptic inhibition in the anterior cingulate cortex (ACC), particularly at inhibitory synapses of cholecystokinin (CCK)-expressing interneurons. This enhanced synaptic inhibition in the ACC was characterized by CSIS-induced loss of presynaptic cannabinoid type-1 receptors (CB1Rs), resulting in excessive axonal calcium influx. Activation of CCK-expressing interneurons or conditional knockdown of CB1R expression in CCK-expressing interneurons specifically reproduced social impairment. In contrast, optogenetic activation of CB1R or administration of CB1R agonists restored sociability in CSIS mice. These results suggest that the CB1R may be an effective therapeutic target for preventing CSIS-induced social impairments by restoring synaptic inhibition in the ACC.

Development of in silico models to guide the experimental characterisation of penile tissue and inform surgical treatment of erectile dysfunction.

This paper presents a computational study to investigate the mechanical properties of human penile tissues. Different experimental testing regimes, namely indentation and plate-compression tests, are compared to establish the most suitable testing regime for establishing the mechanical properties of the different penile tissues. An idealised MRI-based geometry of the penis, containing different tissue layers, is simulated using the finite element (FE) method to enable realistic predictions of the deformation of the penis. Unlike the linear elastic models used in the literature to-date, hyperelastic isotropic/anisotropic material models are used to capture material nonlinearity and anisotropy. The influence of material properties, morphological variations, material nonlinearity and anisotropy are investigated. Moreover, the implantation of an inflatable penile prosthesis (IPP) is simulated to assess the effects of the implantation procedure, material nonlinearity, and anisotropy on tissue stresses. The results indicate that the interior layers of the penis do not affect the overall stiffness of the penis in the indentation test, while the plate-compression test is able to capture the effects of these layers. Tunica Albuginea (TA) is found to have the most significant contribution to the total stiffness of the penis under load. It can also be observed that buckling occurs in the septum of the penis during the compression tests, and different morphologies dictate different compressive behaviours. There is a clear need for future experimental studies on penile tissues given the lack of relevant test data in the literature. Based on this study, plate-compression testing would offer the most insightful experimental data for such tissue characterisation.

Radiation exposure in multiple hereditary exostoses: A retrospective review.

Background: Exposure to ionizing radiation in patients with Multiple Hereditary Exostoses (MHE) is inevitable and necessary for the diagnosis and treatment of MHE. Radiation exposure has many potentially dangerous consequences, including the increased risk of developing cancer. This is especially concerning in the pediatric patient population since children are more likely to develop adverse effects from radiation than adults. This study aimed to quantify radiation exposure over a five-year period among patients diagnosed with MHE since such information is not currently available in the literature. Methods: Diagnostic radiographs, computed tomography (CT) scans, nuclear medicine studies, and intraoperative fluoroscopy exposures were analyzed for radiation exposure in 37 patients diagnosed with MHE between 2015 and 2020. Results: Thirty-seven patients with MHE underwent 1200 imaging studies, 976 of which were related to MHE and 224 unrelated to MHE. The mean estimated MHE cumulative radiation dose per patient was 5.23 mSv. Radiographs related to MHE contributed the most radiation. Patients from the ages of 10- to 24-years-old received the most imaging studies and exposure to ionizing radiation, especially compared to those under age 10 (P = 0.016). The 37 patients also received a total of 53 surgical-excision procedures, with a mean of 1.4 procedures per person. Conclusions: MHE patients are exposed to increased levels of ionizing radiation secondary to serial diagnostic imaging, with those ages 10-24 years old being exposed to significantly higher doses of radiation. Because pediatric patients are more sensitive to radiation exposure and are at an overall higher risk, the use of radiographs should always be justified in those patients.

Optogenetic polymerization and assembly of electrically functional polymers for modulation of single-neuron excitability.

Ionic conductivity and membrane capacitance are two foundational parameters that govern neuron excitability. Conventional optogenetics has emerged as a powerful tool to temporarily manipulate membrane ionic conductivity in intact biological systems. However, no analogous method exists for precisely manipulating cell membrane capacitance to enable long-lasting modulation of neuronal excitability. Genetically targetable chemical assembly of conductive and insulating polymers can modulate cell membrane capacitance, but further development of this technique has been hindered by poor spatiotemporal control of the polymer deposition and cytotoxicity from the widely diffused peroxide. We address these issues by harnessing genetically targetable photosensitizer proteins to assemble electrically functional polymers in neurons with precise spatiotemporal control. Using whole-cell patch-clamp recordings, we demonstrate that this optogenetic polymerization can achieve stepwise modulation of both neuron membrane capacitance and intrinsic excitability. Furthermore, cytotoxicity can be limited by controlling light exposure, demonstrating a promising new method for precisely modulating cell excitability.

Expanding the NGLY1 deficiency phenotype: Case report of an atypical patient.

NGLY1 deficiency is a rare congenital disorder of deglycosylation with a unique constellation of symptoms that include hypo- or alacrima, movement disorder, epilepsy, and severe intellectual disability (OMIM #615273). Here we report a patient with NGLY1 deficiency whose clinical presentation lacks many of the features associated with the disease and has a much milder intellectual disability than had been previously reported, expanding the phenotypic spectrum.

Social dynamics of core members in mixed-species bird flocks change across a gradient of foraging habitat quality.

Social associations within mixed-species bird flocks can promote information flow about food availability and provide predator avoidance benefits. The relationship between flocking propensity, foraging habitat quality, and interspecific competition can be altered by human-induced habitat degradation. Here we take a close look at sociality within two ecologically important flock-leader (core) species, the Carolina chickadee (Poecile carolinensis) and tufted titmouse (Baeolophus bicolor), to better understand how degradation of foraging habitat quality affects mixed-species flocking dynamics. We compared interactions of free ranging wild birds across a gradient of foraging habitat quality in three managed forest remnants. Specifically, we examined aspects of the social network at each site, including network density, modularity, and species assortativity. Differences in the social networks between each end of our habitat gradient suggest that elevated levels of interspecific association are more valuable in the habitat with low quality foraging conditions. This conclusion is supported by two additional findings: First, foraging height for the subordinate Carolina chickadee relative to the tufted titmouse decreased with an increase in the number of satellite species in the most disturbed site but not in the other two sites. Second, the chickadee gargle call rate, an acoustic signal emitted during agonistic encounters between conspecifics, was relatively higher at the high-quality site. Collectively, these results suggest an increase in heterospecific associations increases the value of cross-species information flow in degraded habitats.

Understanding the deformation gradient in Abaqus and key guidelines for anisotropic hyperelastic user material subroutines (UMATs).

This tutorial paper provides a step-by-step guide to developing a comprehensive understanding of the different forms of the deformation gradient used in Abaqus, and outlines a number of key issues that must be considered when developing an Abaqus user defined material subroutine (UMAT) in which the Cauchy stress is computed from the deformation gradient. Firstly, we examine the "classical" forms of global and local deformation gradients. We then show that Abaqus/Standard does not use the classical form of the local deformation gradient when continuum elements are used, and we highlight the important implications for UMAT development. We outline the key steps that must be implemented in developing an anisotropic fibre-reinforced hyperelastic UMAT for use with continuum elements and local orientation systems. We also demonstrate that a classical local deformation gradient is provided by Abaqus/Standard if structural (shell and membrane) elements are used, and by Abaqus/Explicit for all element types. We emphasise, however, that the majority of biomechanical simulations rely on the use of continuum elements with a local coordinate system in Abaqus/Standard, and therefore the development of a hyperelastic UMAT requires an in-depth and precise understanding of the form of the non-classical deformation gradient provided as input by Abaqus. Several worked examples and case studies are provided for each section, so that the details and implications of the form of the deformation gradient can be fully understood. For each worked example in this tutorial paper the source files and code (Abaqus input files, UMATs, and Matlab script files) are provided, allowing the reader to efficiently explore the implications of the form of the deformation gradient in the development of a UMAT.

Size-Controlled and Shelf-Stable DNA Particles for Production of Lentiviral Vectors.

Polyelectrolyte complex particles assembled from plasmid DNA (pDNA) and poly(ethylenimine) (PEI) have been widely used to produce lentiviral vectors (LVVs) for gene therapy. The current batch-mode preparation for pDNA/PEI particles presents limited reproducibility in large-scale LVV manufacturing processes, leading to challenges in tightly controlling particle stability, transfection outcomes, and LVV production yield. Here we identified the size of pDNA/PEI particles as a key determinant for a high transfection efficiency with an optimal size of 400-500 nm, due to a cellular-uptake-related mechanism. We developed a kinetics-based approach to assemble size-controlled and shelf-stable particles using preassembled nanoparticles as building blocks and demonstrated production scalability on a scale of at least 100 mL. The preservation of colloidal stability and transfection efficiency was benchmarked against particles generated using an industry standard protocol. This particle manufacturing method effectively streamlines the viral manufacturing process and improves the production quality and consistency.

Adaptable transmitter for discrete and continuous variable quantum key distribution.

We present a versatile transmitter capable of performing both discrete variable and continuous variable quantum key distribution protocols (DV-QKD and CV-QKD, respectively). Using this transmitter, we implement a time-bin encoded BB84 DV-QKD protocol over a physical quantum channel of 47 km and a GG02 CV-QKD protocol with true local oscillator over a 10.5 km channel, achieving secret key rates of 4.1 kbps and 1 Mbps for DV- and CV-QKD, respectively. The reported transmitter scheme is particularly suitable for re-configurable optical networks where the QKD protocol is selected to optimize the performance according to the parameters of the links.

Postoperative facial palsy after pediatric posterior fossa tumor resection.

OBJECTIVE: Facial palsy can be caused by masses within the posterior fossa and is a known risk of surgery for tumor resection. Although well documented in the adult literature, postoperative facial weakness after posterior fossa tumor resection in pediatric patients has not been well studied. The objective of this work was to determine the incidence of postoperative facial palsy after tumor surgery, and to investigate clinical and radiographic risk factors. METHODS: A retrospective analysis was conducted at a single large pediatric hospital. Clinical, radiographic, and histological data were examined in children who were surgically treated for posterior fossa tumors between May 1, 1994, and June 1, 2011. The incidence of postoperative facial weakness was documented. A multivariate logistic regression model was used to analyze the predictive ability of clinicoradiological variables for facial weakness. RESULTS: A total of 163 patients were included in this study. The average age at surgery was 7.4 ± 4.7 years, and tumor pathologies included astrocytoma (44%), medulloblastoma (36%), and ependymoma (20%). The lesions of 27 patients (17%) were considered high grade in nature. Thirteen patients (8%) exhibited preoperative symptoms of facial palsy. The overall incidence of postoperative facial palsy was 26% (43 patients), and the incidence of new postoperative facial palsy in patients without preoperative facial weakness was 20% (30 patients). The presence of a preoperative facial palsy had a large and significant effect in univariate analysis (OR 11.82, 95% CI 3.07-45.44, p < 0.01). Multivariate logistic regression identified recurrent operation (OR 4.45, 95% CI 1.49-13.30, p = 0.01) and other preoperative cranial nerve palsy (CNP; OR 3.01, 95% CI 1.24-7.29, p = 0.02) as significant risk factors for postoperative facial weakness. CONCLUSIONS: Facial palsy is a risk during surgical resection of posterior fossa brain tumors in the pediatric population. The study results suggest that the incidence of new postoperative facial palsy can be as high as 20%. The presence of preoperative facial palsy, an operation for recurrent tumor, and the presence of other preoperative CNPs were found to be significant risk factors for postoperative facial weakness.

Technical note: Evaluation of a commercial on-farm milk leukocyte differential tester to identify subclinical mastitis cases in dairy cows.

The objective of this study was to validate the precision and accuracy of a milk leukocyte differential tester to identify subclinical mastitis cases in dairy cows. Milk samples from individual quarters (n = 320) of 80 Holstein cows were aseptically collected and analyzed in this study. Each sample was divided into 2 replicate samples after mixing. One replicate was analyzed for somatic cell count (SCC) using the current gold standard of flow cytometry immediately after milking. The second sample was evaluated using the on-farm milk leukocyte differential tester directly after milking, where total leukocyte count (TLC; cells/mL) was obtained. The SCC and TLC were used to calculate somatic cell score (SCS) and TLC score [TLS = log2 (TLC/100,000) + 3]. Two subclinical mastitis thresholds were set: >200,000 (low) and >400,000 (high) cells/mL. First, precision was determined between the 2 methods. Total leukocyte count and calculated TLS from the milk leukocyte differential device were compared with the gold standard using correlation and regression coefficient of determination analyses. Correlation coefficients (r) were 0.97 for TLC and SCC and 0.90 for TLS and SCS. The coefficient of determination for regression (R2) was 0.94 for TLC and SCC and 0.80 for TLS and SCS. Slopes of regression for scores and measures were 0.36 [95% confidence interval (CI): 0.35-0.37] and 0.69 (CI: 0.65-0.73), respectively; both were significantly different from 1. Sensitivity, specificity, and diagnostic accuracy were calculated for correct diagnosis of the 2 SCC thresholds using the gold standard as reference. The sensitivity of the on-farm test was 58% (95% CI: 44 to 71%) and 73% (95% CI: 56 to 86%) for the low and high thresholds, respectively. The specificities for the on-farm test were 100% (95% CI: 99 to 100%) and 100% (95% CI: 98 to 100%) for the low and high thresholds, respectively. Subclinical diagnosis accuracies were 93% (95% CI: 89 to 95%) and 96% (95% CI: 92 to 98%) for the low and high thresholds, respectively. The on-farm milk leukocyte differential tester was precise but not overall accurate for total cell counts; it had high specificity and accuracy for diagnosis compared with a standard diagnostic tool. These results suggest that the tested system is a promising technology to detect subclinical mastitis on-farm.

An endocannabinoid-regulated basolateral amygdala-nucleus accumbens circuit modulates sociability.

Deficits in social interaction (SI) are a core symptom of autism spectrum disorders (ASDs); however, treatments for social deficits are notably lacking. Elucidating brain circuits and neuromodulatory signaling systems that regulate sociability could facilitate a deeper understanding of ASD pathophysiology and reveal novel treatments for ASDs. Here we found that in vivo optogenetic activation of the basolateral amygdala-nucleus accumbens (BLA-NAc) glutamatergic circuit reduced SI and increased social avoidance in mice. Furthermore, we found that 2-arachidonoylglycerol (2-AG) endocannabinoid signaling reduced BLA-NAc glutamatergic activity and that pharmacological 2-AG augmentation via administration of JZL184, a monoacylglycerol lipase inhibitor, blocked SI deficits associated with in vivo BLA-NAc stimulation. Additionally, optogenetic inhibition of the BLA-NAc circuit markedly increased SI in the Shank3B-/- mouse, an ASD model with substantial SI impairment, without affecting SI in WT mice. Finally, we demonstrated that JZL184 delivered systemically or directly to the NAc also normalized SI deficits in Shank3B-/- mice, while ex vivo JZL184 application corrected aberrant NAc excitatory and inhibitory neurotransmission and reduced BLA-NAc-elicited feed-forward inhibition of NAc neurons in Shank3B-/- mice. These data reveal circuit-level and neuromodulatory mechanisms regulating social function relevant to ASDs and suggest 2-AG augmentation could reduce social deficits via modulation of excitatory and inhibitory neurotransmission in the NAc.

Pro-Oxidative and Proinflammatory Effects After Traveling From Los Angeles to Beijing: A Biomarker-Based Natural Experiment.

BACKGROUND: Exposure to air pollution increases cardiovascular morbidity and mortality. Preventing chronic cardiovascular diseases caused by air pollution relies on detecting the early effects of pollutants on the risk of cardiovascular disease development, which is limited by the lack of sensitive biomarkers. We have previously identified promising biomarkers in experimental animals but comparable evidence in humans is lacking. METHODS: Air pollution is substantially worse in Beijing than in Los Angeles. We collected urine and blood samples from 26 nonsmoking, healthy adult residents of Los Angeles (mean age, 23.8 years; 14 women) before, during, and after spending 10 weeks in Beijing during the summers of 2014 and 2015. We assessed a panel of circulating biomarkers indicative of lipid peroxidation and inflammation. Personal exposure to polycyclic aromatic hydrocarbons (PAHs), a group of combustion-originated air pollutants, was assessed by urinary PAH metabolite levels. RESULTS: Urinary concentrations of 4 PAH metabolites were 176% (95% CI, 103% to 276%) to 800% (95% CI, 509% to 1780%) greater in Beijing than in Los Angeles. Concentrations of 6 lipid peroxidation biomarkers were also increased in Beijing, among which 5-, 12-, and 15-hydroxyeicosatetraenoic acid and 9- and 13-hydroxyoctadecadienoic acid levels reached statistical significance (false discovery rate <5%), but not 8-isoprostane (20.8%; 95% CI, -5.0% to 53.6%). The antioxidative activities of paraoxonase (-9.8%; 95% CI, -14.0% to -5.3%) and arylesterase (-14.5%; 95% CI, -22.3% to -5.8%) were lower and proinflammatory C-reactive protein (101%; 95% CI, 3.3% to 291%) and fibrinogen (48.3%; 95% CI, 4.9% to 110%) concentrations were higher in Beijing. Changes in all these biomarkers were reversed, at least partially, after study participants returned to Los Angeles. Changes in most outcomes were associated with urinary PAH metabolites (P<0.05). CONCLUSIONS: Traveling from a less-polluted to a more-polluted city induces systemic pro-oxidative and proinflammatory effects. Changes in the levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid and 9- and 13-hydroxyoctadecadienoic acid as well as paraoxonase and arylesterase activities in the blood, in association with exposures to PAH metabolites, might have important implications in preventive medicine as indicators of increased cardiovascular risk caused by air pollution exposure.

Dynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states.

Acquisition and extinction of learned fear responses utilize conserved but flexible neural circuits. Here we show that acquisition of conditioned freezing behavior is associated with dynamic remodeling of relative excitatory drive from the basolateral amygdala (BLA) away from corticotropin releasing factor-expressing (CRF+) centrolateral amygdala neurons, and toward non-CRF+ (CRF-) and somatostatin-expressing (SOM+) neurons, while fear extinction training remodels this circuit back toward favoring CRF+ neurons. Importantly, BLA activity is required for this experience-dependent remodeling, while directed inhibition of the BLA-centrolateral amygdala circuit impairs both fear memory acquisition and extinction memory retrieval. Additionally, ectopic excitation of CRF+ neurons impairs fear memory acquisition and facilities extinction, whereas CRF+ neuron inhibition impairs extinction memory retrieval, supporting the notion that CRF+ neurons serve to inhibit learned freezing behavior. These data suggest that afferent-specific dynamic remodeling of relative excitatory drive to functionally distinct subcortical neuronal output populations represents an important mechanism underlying experience-dependent modification of behavioral selection.

Comparing dairy farm milk yield and components, somatic cell score, and reproductive performance among United States regions using summer to winter ratios.

Heat stress abatement is a challenge for dairy producers in the United States, especially in the southern states. Thus, managing heat stress is critical to maintain dairy cow performance in the summer. The ability to employ a metric to measure heat stress and evaluate abatement strategies may benefit dairy producers by providing meaningful feedback on the effectiveness of current and future management strategies with the goal of improving heat stress management. Therefore, this study aimed to explore the use of the summer to winter performance ratio metric to quantify and compare farm performance variables among regions of the United States. Monthly performance data recorded by the Dairy Herd Improvement Association from 2007 to 2016, for all US Dairy Herd Improvement Association herds processing records through Dairy Records Management Systems (Raleigh, NC), were obtained. Season dates were based on the astronomical definition of the Northern Hemisphere with summer as June 21 to September 21 and winter as December 21 to March 19. States were grouped into regions based on climate zone classification. Performance records included a total of 16,573 herds [Northeast (n = 7,955), Midwest (n = 6,555), Northern Plains (n = 305), Southeast (n = 1,370), and Southern Plains (n = 388) regions]. Herd test day performance variables energy-corrected milk, somatic cell score, milk fat and protein percentage, conception rate, heat detection rate, and pregnancy rate in summer and winter were used to calculate summer to winter ratios for each region. The MIXED procedure of SAS 9.4 (SAS Institute Inc., Cary, NC) was used to compare test day performance variables. The effects of year, mean days in milk, mean 150-d milk, mean herd size, and number of milkings per day were included as covariates in the models. Dairy cattle performance in all climate regions was negatively affected by summer heat stress, but some regions greater than others. A difference was also observed among regions when comparing summer to winter ratios for each performance parameter. This indicates that summer performance varies by climate region identified by the summer to winter ratio and demonstrates usefulness of the metric to monitor degree of heat stress based on performance.

Novel Surgical and Radiologic Risk Factors for Progression or Recurrence of Pediatric Pilocytic Astrocytoma.

INTRODUCTION: Pilocytic astrocytomas (PA) are a common, benign childhood tumor known for their slow growth rates and excellent prognosis. The aim of our study was to characterize patient, tumor, and imaging-related risk factors for recurrence and progression of disease. METHODS: We identified 116 patients with PA who underwent surgery at our institution between 2000 and 2015. Data were collected retrospectively from the clinical charts. RESULTS: The mean age at resection was 7 ± 5 years (range 0.5-31) and mean follow-up was 6 ± 3 years. Initial resection was complete in 33 patients (29%), subtotal in 78 patients (67%), and biopsy in 5 patients (4%). A total of 45/116 (40%) patients experienced either recurrence or progression after initial resection with a mean time to recurrence or progression of 2.2 years. Bivariate analysis identified subtotal resection, tumor location, age at diagnosis, and imaging features (i.e., T2 invasion, exophytic component, hemorrhage, and solid tumors) as factors significantly associated with recurrence or progression (p < 0.05). Conversely, PAs that were completely resected, predominately cystic, and located in the cerebellum were significantly associated with no recurrence or progression (p < 0.05). Multivariate regression analysis narrowed down 4 robust risk factors: extent of resection, T2 invasion, predominantly solid lesions, and presence of an exophytic component (p < 0.05). CONCLUSION: Total surgical removal of PA has been the most important prognostic factor for the clinical course of PA. Our study reveals additional risk factors for the recurrence or progression of disease: tumor invasion, solid composition, and tumors with an exophytic component.