Cortical Morphology and White Matter Tractography of Three Phylogenetically Distant Primates: Evidence for a Simian Elaboration.

Comparative neuroimaging has been used to identify changes in white matter architecture across primate species phylogenetically close to humans, but few have compared the phylogenetically distant species. Here, we acquired postmortem diffusion imaging data from ring-tailed lemurs (Lemur catta), black-capped squirrel monkeys (Saimiri boliviensis), and rhesus macaques (Macaca mulatta). We were able to establish templates and surfaces allowing us to investigate sulcal, cortical, and white matter anatomy. The results demonstrate an expansion of the frontal projections of the superior longitudinal fasciculus complex in squirrel monkeys and rhesus macaques compared to ring-tailed lemurs, which correlates with sulcal anatomy and the lemur's smaller prefrontal granular cortex. The connectivity of the ventral pathway in the parietal region is also comparatively reduced in ring-tailed lemurs, with the posterior projections of the inferior longitudinal fasciculus not extending toward parietal cortical areas as in the other species. In the squirrel monkeys we note a very specific occipito-parietal anatomy that is apparent in their surface anatomy and the expansion of the posterior projections of the optical radiation. Our study supports the hypothesis that the connectivity of the prefrontal-parietal regions became relatively elaborated in the simian lineage after divergence from the prosimian lineage.

U-net model for brain extraction: Trained on humans for transfer to non-human primates.

Brain extraction (a.k.a. skull stripping) is a fundamental step in the neuroimaging pipeline as it can affect the accuracy of downstream preprocess such as image registration, tissue classification, etc. Most brain extraction tools have been designed for and applied to human data and are often challenged by non-human primates (NHP) data. Amongst recent attempts to improve performance on NHP data, deep learning models appear to outperform the traditional tools. However, given the minimal sample size of most NHP studies and notable variations in data quality, the deep learning models are very rarely applied to multi-site samples in NHP imaging. To overcome this challenge, we used a transfer-learning framework that leverages a large human imaging dataset to pretrain a convolutional neural network (i.e. U-Net Model), and then transferred this to NHP data using a small NHP training sample. The resulting transfer-learning model converged faster and achieved more accurate performance than a similar U-Net Model trained exclusively on NHP samples. We improved the generalizability of the model by upgrading the transfer-learned model using additional training datasets from multiple research sites in the Primate Data-Exchange (PRIME-DE) consortium. Our final model outperformed brain extraction routines from popular MRI packages (AFNI, FSL, and FreeSurfer) across a heterogeneous sample from multiple sites in the PRIME-DE with less computational cost (20 s~10 min). We also demonstrated the transfer-learning process enables the macaque model to be updated for use with scans from chimpanzees, marmosets, and other mammals (e.g. pig). Our model, code, and the skull-stripped mask repository of 136 macaque monkeys are publicly available for unrestricted use by the neuroimaging community at https://github.com/HumanBrainED/NHP-BrainExtraction.

A collaborative resource platform for non-human primate neuroimaging.

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field .

MAST CELL TUMORS IN CHEETAH (ACINONYX JUBATUS): A CASE SERIES.

Mast cell tumors in nondomestic felids are rarely reported and their biological characteristics are not well described. A retrospective review of the pathology records of 52 zoo-housed cheetahs (Acinonyx jubatus) identified five cases of mast cell tumor, involving four closely related individuals. The age at initial presentation varied from 14 mo to 6 yr. Four cases presented as solitary or multiple cutaneous masses that were mostly slow growing, up to 20 mm diameter, and predominantly nonulcerated. The diagnosis was made by fine needle aspiration cytology of a lesion in one case and by excisional biopsy in the others. Histopathologically, the lesions resembled low- to intermediate-grade canine mast cell tumors, with variations in the degree of anisocytosis and anisokaryosis. Surgical excision was incomplete for 80% of the cutaneous lesions, but local recurrence was not observed in any case. One animal with cutaneous lesions subsequently developed fatal visceral mastocytosis involving the spleen, liver, and adrenal gland. There was no evidence of lymph node invasion or paraneoplastic gastrointestinal signs in any of the cases.

Chromium and cobalt ion concentrations in blood and serum following various types of metal-on-metal hip arthroplasties: a literature overview.

BACKGROUND AND PURPOSE: Widely different metal ion concentrations in blood and serum have been reported with metal-on-metal (MoM) implants. We reviewed the literature on blood and serum ion concentrations of chromium (Cr) and cobalt (Co) following various MoM hip arthroplasties. METHODS: Studies were searched for in the Medline database, Embase, and the Cochrane Database of Systematic Reviews. Highest mean or median ion concentrations of Cr and Co after a minimum of 1 year of follow-up were extracted and grouped according to sample- and articulation type, and average values were calculated. RESULTS: 43 studies were included and 16 different MoM implants were identified. For the different types of bearings, average ion concentrations and range were calculated from the mean or median ion concentration. The average Cr concentration ranged between 0.5 and 2.5 µg/L in blood and between 0.8 and 5.1 µg/L in serum. For Co, the range was 0.7-3.4 µg/L in blood and 0.3-7.5 µg/L in serum. INTERPRETATION: When the average blood ion concentrations calculated for the different implants, together with the concentrations measured in the individual studies, were compared with the upper acceptable limit for Cr and Co in blood, no clear pattern was recognized. Furthermore, we were unable to detect any clear difference in ion concentrations between different types of implants (THA and resurfacing).

A map of white matter tracts in a lesser ape, the lar gibbon.

The recent development of methods for constructing directly comparable white matter atlases in primate brains from diffusion MRI allows us to probe specializations unique to humans, great apes, and other primate taxa. Here, we constructed the first white matter atlas of a lesser ape using an ex vivo diffusion-weighted scan of a brain from a young adult (5.5 years) male lar gibbon. We find that white matter architecture of the gibbon temporal lobe suggests specializations that are reminiscent of those previously reported for great apes, specifically, the expansion of the arcuate fasciculus and the inferior longitudinal fasciculus in the temporal lobe. Our findings suggest these white matter expansions into the temporal lobe were present in the last common ancestor to hominoids approximately 16 million years ago and were further modified in the great ape and human lineages. White matter atlases provide a useful resource for identifying neuroanatomical differences and similarities between humans and other primate species and provide insight into the evolutionary variation and stasis of brain organization.

Variation in spatial dependencies across the cortical mantle discriminates the functional behaviour of primary and association cortex.

Recent theories of cortical organisation suggest features of function emerge from the spatial arrangement of brain regions. For example, association cortex is located furthest from systems involved in action and perception. Association cortex is also 'interdigitated' with adjacent regions having different patterns of functional connectivity. It is assumed that topographic properties, such as distance between regions, constrains their functions, however, we lack a formal description of how this occurs. Here we use variograms, a quantification of spatial autocorrelation, to profile how function changes with the distance between cortical regions. We find function changes with distance more gradually within sensory-motor cortex than association cortex. Importantly, systems within the same type of cortex (e.g., fronto-parietal and default mode networks) have similar profiles. Primary and association cortex, therefore, are differentiated by how function changes over space, emphasising the value of topographical features of a region when estimating its contribution to cognition and behaviour.

Value of routine blood tests for prediction of mortality risk in hip fracture patients.

BACKGROUND: There is a 5- to 8-fold increased risk of mortality during the first 3 months after a hip fracture. Several risk factors are known. We studied the predictive value (for mortality) of routine blood tests taken on admission. METHODS: 792 hip fracture patients were included prospectively; blood tests were taken on admission. Follow-up data on mortality were obtained from the civil registration system. Patients were divided into 2 groups based on whether they had survived at least 90 days after the hip fracture. To estimate which laboratory tests could be used to predict outcome, we used receiver operation characteristic (ROC) curves. RESULTS: 3-month mortality could be predicted with 69% accuracy from the level of plasma creatinine in standard admission blood tests. The mortality in patients with elevated levels of creatinine was almost 3-fold that of the patients with normal creatinine. Mortality was also associated with age, low blood hemoglobin, high plasma potassium, and low plasma albumin levels. INTERPRETATION: Our findings could be of use in identifying patients who might benefit from increased attention perioperatively.

Is mortality after hip fracture associated with surgical delay or admission during weekends and public holidays? A retrospective study of 38,020 patients.

BACKGROUND AND PURPOSE: Hip fractures are associated with high mortality, but the cause of this is still not entirely clear. We investigated the effect of surgical delay, weekends, holidays, and time of day admission on mortality in hip fracture patients. PATIENTS AND METHODS: Using data from the Danish National Indicator Project, we identified 38,020 patients admitted from 2003 to 2010. Logistic regression analysis was used to study the association between sex, age, weekend or holiday admission, night-time admission, time to surgery, and ASA score on the one hand and mortality on the other. RESULTS: The risk of death in hospital increased with surgical delay (odds ratio (OR) = 1.3 per 24 h of delay), ASA score (OR (per point added) = 2.3), sex (OR for men 2.2), and age (OR (per 5 years) = 1.4). The mortality rate for patients admitted during weekends or public holidays, or at night, was similar to that found for those admitted during working days. INTERPRETATION: Minimizing surgical delay is the most important factor in reducing mortality in hip fracture patients.

Pre-fracture medication use as a predictor of 30-day mortality in hip fracture patients: an analysis of 141,201 patients.

PURPOSE: To evaluate the predictive value of pre-fracture medication usage on 30-day mortality following a hip fracture. METHODS: Information on age, sex, fracture type, time of death and Charlson co-morbidity index (CCI) was collected from the Danish National Patient Registry on all patients above 60 years, sustaining a hip fracture during the period January 1995 to December 2013. Information on drug usage was obtained from the Danish National Prescription Database. Hazard ratios were calculated with 30-day mortality as the outcome. A univariate and 3 multivariate analyses were conducted with increasing adjustments, starting with age, sex and fracture type, adding co-morbidity and dose in the latter. RESULTS: 141,201 patients were included and a total of 12 drugs/drug groups were identified for analysis. Increased mortality was evident in all analyses for antiarrhythmics, beta blockers, proton pump inhibitors, loop diuretics, opioids, acetaminophen and for psycholeptics. For ACE-inhibitors, increased mortality was found in all analyses, except after adjustment for co-morbidity and dose. For thiazide diuretics, a significantly reduced mortality was evident in all but the univariate analyses while NSAIDs and statins were associated with a significantly reduced mortality in all analyses. For calcium channel blockers, an insignificant decrease was found after adjustment for dose. Further analysis showed a dose-response relationship for all drugs except ACE-inhibitors and calcium channel blockers. CONCLUSION: The study shows a correlation between pre-fracture usage of certain drugs and 30 day mortality after a hip fracture.

Investigation and diagnosis of nontuberculous mycobacteriosis in a captive herd of aoudad (Ammotragus lervia).

An epizootic of nontuberculous mycobacteriosis occurred in a captive herd of aoudad (Ammotragus lervia) over a period of 18 mo. Each of the affected animals was subject to a thorough postmortem examination that included histopathology, tissue concentration and acid-fast staining, aerobic and anaerobic bacterial culture, mycobacterial culture, and real-time polymerase chain reaction specific for Mycobacterium tuberculosis DNA. Histopathologic lesions consistent with pulmonary mycobacteriosis, including the presence of acid-fast bacteria, were identified in two captive adult male aoudad. M. avium was isolated in culture from the pulmonary parenchyma, and M. parafortuitum was isolated from a mesenteric lymph node of a third animal, an adult female, euthanized subsequent to an illness characterized by progressive dyspnea and tachypnea. M. intracellulare was isolated within the bronchial lymph node of a fourth aoudad, an adult female that was euthanized due to chronic weight loss. Diagnostic testing of the 34 individuals in the herd included collection of blood for an interferon-gamma assay, intradermal tuberculin testing, and radiometric fecal culture for M. avium subsp. paratuberculosis. On the basis of this investigation, mycobacteriosis associated with M. bovis, M. tuberculosis, and/or M. avium subsp. paratuberculosis was ruled out and nontuberculous mycobacteriosis was confirmed in this herd.

Re-amputations and mortality after below-knee, through-knee and above-knee amputations.

INTRODUCTION: From January 2013, we changed the surgical strategy in our department and ceased to perform the through-knee amputation (TKA). The primary aim of this study was to investigate re-amputation rates ≤ 90 days after non-traumatic major lower-extremity amputations performed before and after this change of practice. Furthermore, we reported mortality before and after the change of practice. METHODS: All non-traumatic major lower-extremity amputations performed in a single centre in two study periods (before and after the change of practice); 2009-2012 (cohort A) and 2014-2015 (cohort B) were included. Re-amputations and all-cause mortality ≤ 90 days after the index amputations were analysed. RESULTS: Cohort A: Included 180 amputations with 27 below-knee amputations (BKA), 68 TKAs and 85 above-knee amputations (AKA). 86.7% of patients were American Society of Anesthesiologists (ASA) score 3-5. The re-amputation rate ≤ 90 days was 29.6% (95% confidence interval (CI): 12.7-47.3%) after BKA, 33.8% (95% CI: 22.7-45.3%) after TKA, 9.4% (95% CI: 2.9-15.1%) after AKA and 21.6% (95% CI: 15.6-27.6%) overall. The overall mortality ≤ 90 days was 35.2% (95% CI: 26.2-44.2%). Cohort B: Included 116 amputations with 21 BKA and 95 AKA. 92.7% of patients were ASA score 3-5. The re-amputation rate ≤ 90 days was 19.1% (95% CI: 7.7-40.0%) after BKA, 2.1% (95% CI: 0.6-7.4%) after AKA and 5.2% (95% CI: 2.4-10.8%) overall. The overall mortality ≤ 90 days was 32.8% (95% CI: 26.2-44.2%). CONCLUSIONS: The overall re-amputation rate ≤ 90 days following major lower-extremity amputation decreased significantly from 22% to 5% after cessation of the TKA procedures, but mortality remained unchanged. FUNDING: none. TRIAL REGISTRATION: not relevant.

Anesthesia and use of a sling system to facilitate transvaginal laparoscopy in a black rhinoceros (Diceros bicornis minor).

Transvaginal laparoscopy to allow assessment of ovarian pathology and to attempt retrieval of oocytes was facilitated in a captive, female black rhinoceros (Diceros bicornis minor) through the use of a sling on two separate occasions. Following induction of anesthesia with an opioid-based combination, the rhinoceros was intubated and maintained on isoflurane in oxygen. The use of the sling and volume controlled inhalation anesthesia allowed for maintenance of appropriate anatomic positioning, analgesia, and insufflation of the abdominal cavity for laparoscopy during both procedures.

Morbidity and mortality associated with Arcanobacterium pyogenes in a group of captive blackbuck (Antilope cervicapra).

Arcanobacterium pyogenes was associated with necrotizing pneumonia; mandibular osteomyelitis; peritonitis; and hepatic, pulmonary, renal, and subcutaneous abscessation in a group of captive blackbuck (Antilope cervicapra). Males were more frequently (73.3%) affected than females. Infection with A. pyogenes was fatal or necessitated euthanasia in 15 of 16 (93.7%) cases. Deaths associated with A. pyogenes occurred most frequently (60%) during winter.

Modulation of pituitary-adrenocortical function: decreased secretory episodes and blunted circadian rhythmicity in patients with alcoholic liver disease.

Twenty-four-hour episodic secretion of cortisol was studied in patients with chronic alcoholic liver disease in order to define how and if feedback inhibition of the hypothalamic-pituitary-adrenocortical axis had occurred. The patients had prolonged disappearance rates of endogenous cortisol and corticosteroid-binding globulin-binding capacity was low. Multiple sampling (every 20 min) for levels of free and total plasma cortisol was carried out. Mean 24-h total and free plasma cortisol levels were not significantly different from normal, although the mean percentage of free cortisol was high. Cortisol secretion was decreased, as judged by urinary free cortisol values and the percentage of time that secretory activity occurred. Circadian rhythmicity of plasma cortisol levels appeared to be normal, but the amplitude of rhythmicity was decreased. Modulation of cortisol secretion in liver disease patients was shown by fewer secretory peaks and decreased secretory time during 24-hr studies. In the subjects studied, the numbers of secretory episodes and the duration of secretory time correlated positively with levels of corticosteroid-binding globulin and negatively with the half-time of cortisol in plasma. These studies suggest that feed-back inhibition modifies bot the frequency and the amplitude of cortisol secretion in patients with liver disease while the underlying circadian rhythm is preserved.

Pituitary-adrenocortical function in chronic renal failure: blunted suppression and early escape of plasma cortisol levels after intravenous dexamethasone.

The response to iv dexamehasone was studied in patients with chronic renal failure in whom resistance to suppression of plasma cortisol levels after oral steroid had been reported previously. One milligram of dexamethasone was given iv at 2300 h, and plasma cortisol levels were measured every 20 min between 0500-1000h in patients with renal failure, normal controls, and patients with pituitary-dependent Cushing's syndrome. Normal subjects showed a decrease in mean plasma cortisol levels to less than 3 micrograms/dl; patients with Cushing's syndrome showed no suppression of cortisol secretory activity during the sampling period. In renal failure patients, morning cortisol levels fell to values lower than those achieved when the 1-mg dose was given orally or when the steroid was not given, but did not suppress to the levels seen in normals. Early resumption of cortisol secretion occurred in four of five renal failure patients during the 6-11 h after dexamethasone administration. These studies show that iv dexamethasone is more effective than the oral steroid in suppressing pituitary-adrenocortical activity in renal failure patients. However, the incomplete suppression and early resumption of cortisol secretion which are present in chronic renal failure patients even after iv dexamethasone support the suggestion that they have disordered feedback control of the hypothalamic-pituitary-adrenocortical axis.

Methicillin-resistant Staphylococcus aureus in a cystic fibrosis unit.

Methicillin-resistant Staphylococcus aureus (MRSA) infection in a cystic fibrosis (CF) unit was investigated. Two typing methods, phage-typing and restriction fragment length polymorphism (RFLP) by pulsed-field gel electrophoresis (PFGE) and phylogenetic analysis, showed that nonsocomial transmission of MRSA from the general hospital population had occurred. One instance of possible transmission between two patients was identified. However, transmission between two family members did not occur indicating a minimal risk of MRSA acquisition from social contact compared with hospital admission. This study supports policies for limiting CF-patient admission to hospital but transmission of MRSA does not appear to be a reason for limiting social contact with other CF patients.

Molecular epidemiology of Burkholderia cepacia in two Australian cystic fibrosis centres.

Forty individual patient sputum isolates of Burkholderia cepacia from two Australian cystic fibrosis (CF) centres more than 100 km apart were genotyped using pulsed-field gel electrophoresis (PFGE) with XbaI restriction enzyme digestion. Hospital 1 had an endemic strain with 19 of 20 isolates being closely related. This centre does not implement an inpatient segregation policy for its paediatric patients who constitute the majority of those colonized with B. cepacia. Hospital 2 did not have a single endemic strain; there were two different sibling clusters and a third cluster involving a cohabiting couple, but all other patients had unique isolates. One patient at Hospital 2 carried an organism closely related to the endemic strain from Hospital 1. Hospital 2 practises segregation of colonized inpatients and also segregation external to the hospital. It would appear that no nosocomial spread of infection is occurring with this policy.

The impact of pan-resistant bacterial pathogens on survival after lung transplantation in cystic fibrosis: results from a single large referral centre.

Reported actuarial one-year survival for patients with cystic fibrosis (CF) after lung transplant is 55-91%. Infection is the most common cause of early death. Colonization with Burkholderia cepacia complex is associated with reduced survival and international lung transplant referral guidelines support individual unit assessment policies for patients colonized with other pan-resistant bacteria. We examined local data on survival after transplant for CF to determine the impact of colonization with pan-resistant bacteria. A retrospective review of all CF patients from Royal Prince Alfred Hospital (RPAH), Sydney, who underwent lung transplantation at St Vincent's Hospital, Sydney, 1989-2002, was performed. Sixty-five patients were listed for lung transplantation with 54 (male: female=29:25) receiving transplants. Of the 11 patients (17%) who died on the waiting list, six were colonized with pan-resistant Pseudomonas aeruginosa. Thirty of the 54 transplanted patients had at least one pan-resistant organism before transplant. In 28 this included P. aeruginosa. Overall one-year survival was 92% with a median survival of 67 months. Overall survival for the pan-resistant group (N = 30) was not significantly different to survival in those with sensitive organisms (N = 24) (Logrank chi square = 1.6, P = 0.2). Three patients colonized with B. cepacia complex pre-transplant survive at 11, 40 and 60 months post-transplant. Infection contributed to 11 of the 18 post-transplant deaths, with pre-transplant-acquired bacterial pathogens responsible in two cases. Patients continued to acquire multiresistant bacteria post-transplantation. Lung transplant survival at St Vincent's Hospital for CF adults from RPAH compares favourably with international benchmarks. Importantly, colonization with pan-resistant bacteria pre-transplant did not appear to adversely affect survival post-transplant.

Detection of persistent vegetative bacteria and amplified viral nucleic acid from in-use testing of gastrointestinal endoscopes.

Hospital-acquired infection attributed to inadequate decontamination of gastrointestinal endoscopes prompted an in use evaluation of recommended procedures. Specimens were obtained from the internal channels of 123 endoscopes before, during and after decontamination by flushing with saline and brushing with a sterile brush, and examined for vegetative bacteria by broth and plate culture. Four endoscopy units were tested; the chemical disinfectants used were: 2% glutaraldehyde in Centres 1 and 2 (automated) and Centre 3 (manual); peracetic acid in Centre 4 (automated). Samples from patients in Centre 1 with known chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1) infection were also examined for viral nucleic acid by ultracentrifugation, nucleic acid extraction, reverse transcription (for RNA) and polymerase chain reaction (PCR). No persistent vegetative bacteria were found following standard manual cleaning and disinfection for 20 min in 2% glutaraldehyde in Centres 2 and 3 (N = 37). At Centre 1, while plate culture yielded no growth, 34% of samples (10/29) grew vegetative bacteria in broth culture after cleaning and disinfection for 20 min in 2% glutaraldehyde. Investigation revealed an error in manual cleaning; no bacteria were detected in 37 samples taken after this was corrected. At Centre 4, despite the use of peracetic acid as a sterilant, three out of 20 (15%) of post decontamination samples grew bacteria; one contained persistent bacteria. HBV and HCV PCR analysis detected viral nucleic acid in three out of four and four out of six samples from viraemic patients undergoing endoscopy in Centre 1 during the period of improper manual washing. After proper cleaning was instituted, samples from nine out of nine HCV viraemic patients were negative. HIV RNA was detected in five of 14 samples taken from endoscopes after use on HIV positive patients but all post decontamination samples were negative. Detection of bacteria in washes from endoscope channels is a useful warning of a breakdown in decontamination practice. Inadequate brushing of internal channels may result in persistent HCV and HBV viral nucleic acid, the significance of which is not clear. These results reinforce the importance of adequate manual cleaning of endoscopes before chemical disinfection.