A comprehensive transcriptional map of primate brain development.

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

Current recommendations on the selection of measures for well-being.

Measures of well-being have proliferated over the past decades. Very little guidance has been available as to which measures to use in what contexts. This paper provides a series of recommendations, based on the present state of knowledge and the existing measures available, of what measures might be preferred in which contexts. The recommendations came out of an interdisciplinary workshop on the measurement of well-being. The recommendations are shaped around the number of items that can be included in a survey, and also based on the differing potential contexts and purposes of data collection such as, for example, government surveys, or multi-use cohort studies, or studies specifically about psychological well-being. The recommendations are not intended to be definitive, but to stimulate discussion and refinement, and to provide guidance to those relatively new to the study of well-being.

Early partial portal venous contrast enhancement in canine CT-Angiography.

Early partial portal vein contrast enhancement (EPoVE) during the late arterial phase is seen in CT angiography of dogs. Previously, it has been a finding attributed to arterioportal vascular anomalies. However, EPoVE may be a normal feature of venous return from abdominal organs. This prospective, descriptive study investigated the origin of EPoVE using four-dimensional CT (4D-CT). Sixteen dogs undergoing 4D-CT for disease of the cranial abdomen were prospectively collected. Regions of interest were placed in the hepatic artery (HA), gastroduodenal vein (GV), extrahepatic portal vein (EHPV) cranial and caudal to the GV, and splenic vein (SV) caudal to its EHPV entry. Times to earliest, partial, full, and maximal vascular enhancement were recorded. A mixed model analysis of variance was used to compare time-to-contrast enhancement between vessels. The number, origin, and time of EPoVE were recorded if visible. A total of 24 EPoVE areas were observed in all dogs. Most dogs had either one (10/16) or two (5/16) areas of EPoVE. The origin of EPoVE was identified in 14 of 24 areas: the GV in five areas, cranial mesenteric vein in four areas, pancreatic branch of SV in three areas, and SV in two areas. The time-to-contrast-enhancement was significantly different for the individual veins compared to the HA. EPoVE during the late arterial phase is a common phenomenon of early portal venous drainage of abdominal organs; it should not be interpreted as pathognomonic for arterioportal vascular anomalies, which should be diagnosed based on additional criteria.

Evaluation of a pre-tied ligature loop for canine total lung lobectomy.

OBJECTIVE: To determine the ability of a pre-tied ligature loop (PLL) to create a seal against physiological airway pressures after total lung lobectomy and report outcomes in dogs requiring lung lobectomy. STUDY DESIGN: Ex vivo experimental randomized study and clinical case study. SAMPLE POPULATION: Thirty cadaveric canine lung lobes and 5 client-owned dogs. METHODS: Thirty canine lung lobes from dogs weighing 22.5-35 kg were randomized to lobectomy with stapler, PLL, or suture ligation. After lobectomy, each bronchial stump was submerged in water, and the mainstem airway pressure was increased to 80 mm Hg. Leakage was compared between techniques. The PLL was subsequently used in 5 dogs (17-25 kg) with neoplastic disease requiring total lung lobectomy. RESULTS: Two stapled and 4 sutured bronchial stumps leaked at supraphysiological pressures >15 mm Hg. One stapled bronchial stump failed at a physiological airway pressure (5 mm Hg). None of the PLL lobectomies leaked. The incidence of bronchial stump failures did not differ among techniques (P = .15). Lung lobectomy was performed successfully with the PLL in 5 clinical cases with no intraoperative or postoperative complications; median follow-up time was 6 months. CONCLUSION: Bronchial ligation with the PLL reliably resisted physiological airway pressures and performed comparably to current standard techniques in cadavers. The PLL provided an adequate air and vascular seal in 5 clinical cases undergoing total lung lobectomy. CLINICAL RELEVANCE: Pre-tied ligature loops provide an alternative method for total lung lobectomy in dogs.

A comparison of fixation methods for supracondylar and distal humeral shaft fractures of the dog and cat.

Retrospective analysis of case records from dogs and cats diagnosed with supracondylar or distal diaphyseal humeral fractures was performed. Complications were compared and outcome was assessed at final follow-up and by owner questionnaire. A total of 37 cases (25 dogs and 12 cats) were included. Methods used consisted of plates and screws or external skeletal fixator (ESF). The ESF was associated with a significantly higher rate of minor complications (14/22) compared with plates and screws (2/15). There was no difference in major or catastrophic complications between fixation methods. Major complications occurred in 4/37 cases and catastrophic complications occurred in 3/37 cases. Good or excellent outcome was achieved in 24/33 of cases. There was no difference in outcome between dogs and cats. Plates and screws or ESF can be successful methods of managing supracondylar and distal diaphyseal humeral fractures in dogs and cats. Prognosis may be more guarded, however, than previously reported.

Comparaison des méthodes de fixation pour les fractures sus-condyliennes et distales de la diaphyse chez le chien et le chat. Une analyse rétrospective des dossiers de cas de chiens et de chats diagnostiqués avec des fractures sus-condyliennes et distales de l'humérus a été réalisée. Les complications ont été comparées et les résultats ont été évalués au suivi final et à l'aide d'un questionnaire rempli par le propriétaire. Trente-sept cas (25 chiens et 12 chats) ont été inclus au total. Les méthodes utilisées comportaient des plaques et des vis ou un fixateur squelettique externe (FSE). Le FSE était associé à un taux significativement supérieur de complications mineures (14/22) comparativement aux plaques et aux vis (2/15). Il n'y avait aucune différence pour les complications majeures ou catastrophiques entre les méthodes de fixation. Des complications majeures se sont produites dans 4/37 cas et des complications majeures se sont produites dans 3/37 cas. Un résultat adéquat ou excellent a été obtenu dans 24/33 des cas. Il n'y avait aucune différence au niveau des résultats entre les chiens et les chats. Les plaques et les vis ou le FSE peuvent être des méthodes réussies de gestion des fractures sus-condyliennes et distales de la diaphyse chez les chiens et les chats. Cependant, le pronostic peut être plus réservé que ce qui avait été précédemment signalé.(Traduit par Isabelle Vallières).

Mechanical properties of 6 finger-trap suture techniques.

OBJECTIVE: To identify the most common methods used by surgeons to place finger-trap sutures (FTS), and determine their influence on the biomechanical properties of constructs. STUDY DESIGN: Questionnaire and experimental study. METHODS: Six commonly used FTS methods (A-F) were identified from literature review and questionnaire. Constructs made with 3-metric nylon suture and 18-French polyurethane esophagostomy tubing were tested in axial loading to failure. Two patterns (B and D) selected based on common use and biomechanical performance were further tested, with 2, 4, and 8 repeats along the tube. Displacement, load, and energy at failure were compared between constructs, and failure mode was video recorded. RESULTS: Patterns E and F were susceptible to slipping (P < .001). Patterns A and D were stiffer than pattern E, and patterns A-D were stiffer than pattern F (P = .012). Patterns A and B had less extension than pattern E and F, and patterns A-D had less extension than pattern F (P = .002). 87.5% of FTS failed by breaking at the first suture knot. The number of repeats had no effect on FTS performance, but catastrophic failure occurred in 2 constructs with 2 repeats. CONCLUSION: The mechanical behavior of suture-tube constructs and failure mode is affected by the FTS pattern. Patterns E and F are not advocated due to suture slippage. The number of repeats may not affect the FTS performance, but a minimum of 4 repeats is recommended. Overall, patterns B, C, and D performed the best in axial loading.

USE OF COMPOSITE MATERIALS AS A COMPONENT OF TUSK FRACTURE MANAGEMENT IN AN ASIAN ELEPHANT (ELEPHAS MAXIMUS) AND AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).

Tusk fractures in Asian (Elephas maximus) and African elephants (Loxodonta africana) can result in damage to the distal end or to longitudinal cracks, potentially progressing to pulpitis. With pulp exposure, endodontic therapy is the treatment of choice, but conservative therapy has sufficed for some elephants. This manuscript describes the use of composite materials as a component of tusk fracture management. A 7-yr-old male Asian elephant fractured the distal end of both tusks with pulp exposure in one. Capping of each tusk with a Kevlar/fiberglass composite prevented further damage, and a modification allowed care of the exposed pulp tissue. A 34-yr-old male African elephant with a longitudinal crack received a carbon fiber/fiberglass composite circumferential wrap to potentially stabilize the crack. Compression of the crack was achieved, but follow-up was truncated due to bacterial pulpitis. Both cases show that composite material allows for lightweight, durable management of tusk fractures with continued radiographic monitoring.

Canine intrahepatic vasculature: is a functional anatomic model relevant to the dog?

OBJECTIVE: To clarify canine intrahepatic portal and hepatic venous system anatomy using corrosion casting and advanced imaging and to devise a novel functional anatomic model of the canine liver to investigate whether this could help guide the planning and surgical procedure of partial hepatic lobectomy and interventional radiological procedures. STUDY DESIGN: Prospective experimental study. ANIMALS: Adult Greyhound cadavers (n = 8). METHODS: Portal and hepatic vein corrosion casts of healthy livers were assessed using computed tomography (CT). RESULTS: The hepatic lobes have a consistent hilar hepatic and portal vein supply with some variation in the number of intrahepatic branches. For all specimens, 3 surgically resectable areas were identified in the left lateral lobe and 2 surgically resectable areas were identified in the right medial lobe as defined by a functional anatomic model. CONCLUSIONS: CT of detailed acrylic casts allowed complex intrahepatic vascular relationships to be investigated and compared with previous studies. Improving understanding of the intrahepatic vascular supply facilitates interpretation of advanced images in clinical patients, the planning and performance of surgical procedures, and may facilitate interventional vascular procedures, such as intravenous embolization of portosystemic shunts. Functional division of the canine liver similar to human models is possible. The left lateral and right medial lobes can be consistently divided into surgically resectable functional areas and partial lobectomies can be performed following a functional model; further study in clinically affected animals would be required to investigate the relevance of this functional model in the dog.

Primary retropharyngeal leiomyosarcoma in a young cat.

Case summary: An Oriental Shorthair cat, aged 1 year and 6 months, developed progressive stridor and a palpable right ventral cervical mass. Fine-needle aspiration of the mass was inconclusive, while thoracic radiography and CT showed no evidence of metastasis. There was initial improvement in stridor with oral doxycycline and prednisolone treatment, but it recurred 4 weeks later and excisional biopsy was performed. Histopathology with immunohistochemistry diagnosed leiomyosarcoma with incomplete surgical margins. Adjunctive radiation therapy was declined. Repeated physical examination and CT 7 months postoperatively documented no evidence of mass recurrence. Relevance and novel information: This is the first reported case of retropharyngeal leiomyosarcoma in a young cat with no evidence of local reoccurrence 7 months following an excisional biopsy.

Integrating In Vitro Biopharmaceutics into Physiologically Based Biopharmaceutic Model (PBBM) to Predict Food Effect of BCS IV Zwitterionic Drug (GSK3640254).

A strategy followed to integrate in vitro solubility and permeability data into a PBBM model to predict the food effect of a BCS IV zwitterionic drug (GSK3640254) observed in clinical studies is described. The PBBM model was developed, qualified and verified using clinical data of an immediate release (IR)-tablet (10-320 mg) obtained in healthy volunteers under fasted and fed conditions. The solubility of GSK3640254 was a function of its ionization state, the media composition and pH, whereas its permeability determined using MDCK cell lines was enhanced by the presence of mixed micelles. In vitro data alongside PBBM modelling suggested that the positive food effect observed in the clinical studies was attributed to micelle-mediated enhanced solubility and permeability. The biorelevant media containing oleic acid and cholesterol in fasted and fed levels enabled the model to appropriately capture the magnitude of the food effect. Thus, by using Simcyp® v20 software, the PBBM model accurately predicted the results of the food effect and predicted data were within a two-fold error with 70% being within 1.25-fold. The developed model strategy can be effectively adopted to increase the confidence of using PBBM models to predict the food effect of BCS class IV drugs.

Radial artery pseudoaneurysm in a Maine Coon cat.

OBJECTIVE: To report the diagnosis and treatment of a radial artery pseudoaneurysm in a cat. STUDY DESIGN: Clinical report. ANIMAL: Maine Coon cat (8-year-old neutered male). METHODS: Ultrasonographic and angiographic examination of a fluctuant, nonpainful, 3 cm × 1.5 cm subcutaneous swelling on the craniomedial distal aspect of the right radius that occurred 40 days after suspected cat bite trauma was consistent with a radial artery pseudoaneurysm. After ligation of the radial artery proximal to the lesion, the pseudoaneurysm was surgically excised. RESULTS: The excised tissue had hemorrhage and fibrin surrounded by a thick fibrous granulating capsule of variably mature fibroblasts and focal areas of inflammatory cells (lymphocytes, plasma cells, and macrophages) consistent with a pseudoaneurysm. Surgical excision resulted in resolution of clinical signs. CONCLUSIONS: Ultrasonography enabled prompt, noninvasive diagnosis of pseudoaneurysm. Angiography or computed tomography may be useful to aid diagnosis and assess the collateral blood supply to the manus before surgical treatment.

Successful percutaneous drainage of a refractory caudal mediastinal paraesophageal abscess in a dog.

OBJECTIVE: To describe a novel technique for paraesophageal abscess drainage in a dog. CASE SUMMARY: A 6-year-old dog presented for pyrexia of unknown origin, subsequently confirmed to be due to a paraesophageal abscess. This was managed by the ultrasound-guided placement of a thoracostomy tube into the abscess, allowing drainage to be performed. This led to clinical resolution and, at an 8-month follow-up, the dog continued to do well. NEW OR UNIQUE INFORMATION PROVIDED: Paraesophageal abscessation is typically managed with surgical intervention, which carries inherent risks and complications. This report describes a novel technique that did not require general anesthesia or invasive surgical intervention, achieving clinical remission without any adverse effects. It also summarizes the current literature available on this condition.

Comparing the accuracy of freehand, fluoroscopically guided and aiming device-assisted drilling in veterinary orthopaedic surgery.

BACKGROUND: Drilling accuracy is essential in the correct positioning of implants and avoidance of iatrogenic damage to surrounding tissues. The use of augmented drilling methods has been documented as an approach to improving the accuracy of drilling. The aim of this study was to compare the accuracy of two augmented drilling methods (fluoroscopically guided and aiming device) to freehand (FH) drilling. METHODS: Three experienced specialist surgeons and three veterinary surgeons without primary orthopaedic experience drilled into synthetic bone towards a target using the three different methods at three different angles (0°, 10° and 20°). The duration of drilling was recorded, and the accuracy of drilling was measured using photographs before and after drilling. RESULTS: The two augmented methods were more accurate than FH drilling in synthetic bone, with the aiming device producing the greatest accuracy. Increased angulation of drilling decreased the drilling accuracy. Surgeon experience did not impact on drilling accuracy. Surgeon inexperience and augmented drilling methods both increased the time taken to drill. CONCLUSION: The use of augmented drilling methods improved the accuracy of drilling, and surgeons should consider their use when drilling in anatomical regions where the margin of error is small.

Investigation of the in vitro antimicrobial activity of triclosan-coated suture material on bacteria commonly isolated from wounds in dogs.

OBJECTIVE: To investigate in vitro effects of triclosan coating of suture materials on the growth of clinically relevant bacteria isolated from wounds in dogs. SAMPLE: 6 types of suture material and 10 isolates each of methicillin-susceptible Staphylococcus pseudintermedius, methicillin-resistant S pseudintermedius, Escherichia coli, and AmpC ß-lactamase and extended-spectrum ß-lactamase-producing E coli from clinical wound infections. PROCEDURES: Isolates were cultured on Mueller-Hinton agar with 3 types of triclosan-coated suture, uncoated counterparts of the same suture types, and positive and negative controls. Zones of inhibition (ZOIs) were measured after overnight incubation. Sustained antimicrobial activity assays were performed with susceptible isolates. The ZOI measurements and durations of sustained antimicrobial activity were compared among suture types and isolates by statistical methods. Suture surface characteristics and bacterial adherence were evaluated qualitatively with scanning electron microscopy. RESULTS: ZOIs were generated only by triclosan-coated materials; triclosan-coated suture had sustained antimicrobial activity (inhibition) for 3 to 29 days against all tested pathogens. The ZOIs around triclosan-coated suture were significantly greater for S pseudintermedius isolates than for E coli isolates. Bacterial adherence to uncoated polyglactin-910 was greatest, followed by triclosan-coated polyglactin-910, and then uncoated monofilament sutures, with least adherence to coated monofilament sutures. CONCLUSIONS AND CLINICAL RELEVANCE: Surface characteristics of suture materials may be as important or more important than triclosan coating for microbial inhibition; however, triclosan coating appeared to affect bacterial adherence for multifilament sutures. Triclosan-coated, particularly monofilament, sutures inhibited pathogens commonly isolated from wounds of dogs, including multidrug-resistant bacteria. Further studies are required to assess clinical efficacy of triclosan-coated suture materials in vivo.

Recruiting and retaining child welfare workers: is preparing social work students enough for sustained commitment to the field?

Graduates of specialized BSW child welfare education programs are more likely to be retained after two years of service in the agency, but many leave at the four year mark. Two studies explored possible reasons for departure at this time. The first study found that graduates of specialized child welfare programs were significantly more likely to engage in best practices in nine areas than workers from other fields. Thus, frustration with practice skill was ruled out as a cause. The second qualitative study found that poor supervision, lack of coworker support, and organizational stress among other variables prompted these high-functioning workers to leave the agency. Suggestions for innovative interventions to enhance retention at this critical juncture are included.

Sequential drilling and drill angulation reduce the accuracy of drill hole start location in a synthetic bone model.

The accuracy of drill hole location is critical for implant placement in orthopaedic surgery. Increasing drill bit size sequentially has been suggested as a method for improving the accuracy of drill hole start location. The aim of this study was to determine whether sequential drilling or drill angulation would alter accuracy of drill hole start location. Three specialist veterinary surgeons drilled holes in synthetic bone models either directly, or with sequentially increasing drill bit sizes. Drilling was performed at 0o, 10o and 20o to perpendicular to the bone models. Three synthetic bone models were used to mimic canine cancellous and cortical bones. Sequential drilling resulted in greater inaccuracy in drill hole location when assessing all drilling angles together. There was no influence of surgeon or synthetic bone density on drilling accuracy. The combination of drill angulation and sequential drilling increased inaccuracy in drill hole start location. We conclude that sequential drilling decreased accuracy of drill hole location in the synthetic bone model when drilling was angled. Inaccuracy associated with the drill hole start location should be taken into account when performing surgery, although the magnitude of inaccuracy is low when compared with other sources of error such as angulation.

Implementation and Preliminary Results of an Emergency Department Nontargeted, Opt-out Hepatitis C Virus Screening Program.

BACKGROUND: Emergency department (ED) visits provide an opportunity for hepatitis C virus (HCV) screening for patients who otherwise might not be tested. We report on a novel nontargeted, opt-out HCV screening and linkage-to-care (LTC) program implemented in an urban ED. METHODS: This is a descriptive analysis from 3 months (November 2016-January 2017) of a nontargeted, opt-out ED HCV screening and LTC program among patients at least 13 years old undergoing phlebotomy for clinical purposes. A multipurpose best practice advisory (BPA) alerted providers to the program and generated order labels. For patients who authorized testing, specimens were drawn in the ED for HCV antibody (Ab) and reflex confirmatory RNA tests. Public health navigators attempted to contact RNA-positive patients and arrange outpatient visits. RESULTS: HCV Ab tests were performed on 3,808 patients, a 6,950% increase from preprogram. The proportion of HCV Ab test positivity was 13.2% (504/3,808, 95% confidence interval [CI] = 12.2%-14.3%) and of those 97.8% (493/504) had a follow-up RNA test performed. A total of 292 were confirmed positive for active infection, for an overall RNA positivity rate of 7.7% (95% CI = 6.8%-8.5%). Of those with active infection, 155 (53%) were outside the Centers for Disease Control and Prevention birth cohort for increased risk for HCV including 46 (15.8%, 95% CI = 11.8%-20.4%) who also did not report injection drug use. Linkage attempts were documented on 223 (76.4%) patients and appointments were scheduled for 102 (38% of attempted). Sixty-six patients attended their LTC visit (22.5% of all RNA-positive patients, 30% of linkage-eligible patients). CONCLUSIONS: Nontargeted opt-out HCV testing can be successfully implemented in an ED setting. A number of patients diagnosed were outside traditional risk groups. Once diagnosed, an ED population may be difficult to engage in care, but a structured interdisciplinary program can successfully link patients to HCV care.

13 C NMR studies of insulin. Part I-Spectral assignments.

Natural abundance 75 MHz 13 C NMR spectral assignments are reported for bovine and porcine zinc insulin in solution. A large number of protein resonances are well resolved, and approximately 80% of these have been assigned to either residue types or to specific sites within the protein. Assignment techniques included consideration of free amino acid or peptide shifts pH studies and comparison of sequence and spectral differences between bovine and porcine insulin, in addition to the use of NMR relaxation times. The DEPT spectral editing technique was also found to be particularly valuable as an assignment aid. This technique allows subspectra containing only CH, CH2 or CH3 carbon types to be generated. The method also produces signal enhancement relative to broad band decoupled 13 C NMR spectra of large proteins which generally have reduced nuclear Overhauser enhancements.

Antioxidant inhibition of oxygen radicals for measurement of total antioxidant capacity in biological samples.

Few methods for assessing total antioxidant capacity (TAC) include both the percentage of inhibition and the length of inhibition in the measurement. Available methods require above ambient constant temperature incubation, reaction preheating, and/or separate assays for testing hydrophilic and hydrophobic samples. We describe a high-throughput method, antioxidant inhibition of oxygen radicals (AIOR), that overcomes these difficulties. AIOR uses peroxyl radicals to trigger a decrease in fluorescence of the indicator molecule, uroporphyrin I, which is delayed by the presence of antioxidants. The area under the curve is measured by a fluorescence spectrophotometer in a 96-well microplate format, and TAC results are expressed as millimole/liter Trolox equivalents. AIOR is performed at ambient temperature and is applicable to samples in either aqueous or common organic solvents. The reaction between uroporphyrin I and the peroxyl radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) was found to be of first-order kinetics with a mean rate constant (k) of 0.0254. Applications to measure antioxidant capacity are demonstrated on individual chemicals and biological samples. The method has good linearity, within- and between-assay precision, and recovery.