Canagliflozin Attenuates PromarkerD Diabetic Kidney Disease Risk Prediction Scores.

PromarkerD is a biomarker-based blood test that predicts kidney function decline in people with type 2 diabetes (T2D) who may otherwise be missed by current standard of care tests. This study examined the association between canagliflozin and change in PromarkerD score (Δ score) over a three-year period in T2D participants in the CANagliflozin cardioVascular Assessment Study (CANVAS). PromarkerD scores were measured at baseline and Year 3 in 2008 participants with preserved kidney function (baseline eGFR ≥60 mL/min/1.73 m2). Generalized estimating equations were used to assess the effect of canagliflozin versus placebo on PromarkerD scores. At baseline, the participants (mean age 62 years, 32% females) had a median PromarkerD score of 3.9%, with 67% of participants categorized as low risk, 14% as moderate risk, and 19% as high risk for kidney function decline. After accounting for the known acute drop in eGFR following canagliflozin initiation, there was a significant treatment-by-time interaction (p < 0.001), whereby participants on canagliflozin had decreased mean PromarkerD scores from baseline to Year 3 (Δ score: -1.0% [95% CI: -1.9%, -0.1%]; p = 0.039), while the scores of those on placebo increased over the three-year period (Δ score: 6.4% [4.9%, 7.8%]; p < 0.001). When stratified into PromarkerD risk categories, participants with high risk scores at baseline who were randomized to canagliflozin had significantly lower scores at Year 3 (Δ score: -5.6% [-8.6%, -2.5%]; p < 0.001), while those on placebo retained high scores (Δ score: 4.5% [0.3%, 8.8%]; p = 0.035). This post hoc analysis of data from CANVAS showed that canagliflozin significantly lowered PromarkerD risk scores, with the effect greatest in those T2D participants who were classified at study entry as at high risk of a subsequent decline in kidney function.

Opinion Dynamics Systems on Barabási-Albert Networks: Biswas-Chatterjee-Sen Model.

A discrete version of opinion dynamics systems, based on the Biswas-Chatterjee-Sen (BChS) model, has been studied on Barabási-Albert networks (BANs). In this model, depending on a pre-defined noise parameter, the mutual affinities can assign either positive or negative values. By employing extensive computer simulations with Monte Carlo algorithms, allied with finite-size scaling hypothesis, second-order phase transitions have been observed. The corresponding critical noise and the usual ratios of the critical exponents have been computed, in the thermodynamic limit, as a function of the average connectivity. The effective dimension of the system, defined through a hyper-scaling relation, is close to one, and it turns out to be connectivity-independent. The results also indicate that the discrete BChS model has a similar behavior on directed Barabási-Albert networks (DBANs), as well as on Erdös-Rènyi random graphs (ERRGs) and directed ERRGs random graphs (DERRGs). However, unlike the model on ERRGs and DERRGs, which has the same critical behavior for the average connectivity going to infinity, the model on BANs is in a different universality class to its DBANs counterpart in the whole range of the studied connectivities.

An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome.

In flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome (BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers, a mesocephalic breed, are predisposed to Upper Airway Syndrome (UAS), a disease whose pathological features overlap with BOAS. Our health screening clinic examined and scored the airways of 401 Norwich terriers by laryngoscopy. Genome-wide association analyses of UAS-related pathologies revealed a genetic association on canine chromosome 13 (rs9043975, p = 7.79x10-16). Whole genome resequencing was used to identify causal variant(s) within a 414 kb critical interval. This approach highlighted an error in the CanFam3.1 dog assembly, which when resolved, led to the discovery of a c.2786G>A missense variant in exon 20 of the positional candidate gene, ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3). In addition to segregating with UAS amongst Norwich Terriers, the ADAMTS3 c.2786G>A risk allele frequency was enriched among the BOAS-susceptible French and (English) Bulldogs. Previous studies indicate that ADAMTS3 loss of function results in lymphoedema. Our results suggest a new paradigm in the understanding of canine upper airway disease aetiology: airway oedema caused by disruption of ADAMTS3 predisposes dogs to respiratory obstruction. These findings will enhance breeding practices and could refine the prognostics of surgical interventions that are often used to treat airway obstruction.

Intraoperative and major postoperative complications and survival of dogs undergoing surgical management of epiglottic retroversion: 50 dogs (2003-2017).

OBJECTIVE: To report intraoperative and major postoperative complications in dogs treated surgically for epiglottic retroversion (ER), compare the incidence of major postoperative complications between procedures, and report survival of surgically treated dogs. STUDY DESIGN: Multi-institutional retrospective study. SAMPLE POPULATION: Fifty dogs treated with 78 procedures. METHODS: Medical records of dogs diagnosed and surgically treated for ER from 2003 to 2017 at 11 institutions were reviewed. Complications were divided into intraoperative and major postoperative complications. RESULTS: Intraoperative complications occurred during 2 of 78 (2.6%) procedures. Thirty-six major postoperative complications were documented in 22 dogs after 36 of 74 (48.7%) procedures. Postoperative complications occurred after 7 of 12 (58.3%) nonincisional epiglottopexy, 23 of 43 (53.5%) incisional epiglottopexy, 2 of 4 (50%) partial epiglottectomy, 2 of 12 (16.7%) subtotal epiglottectomy, and 2 of 3 (66.7%) other surgical procedures. Epiglottopexy failure was the most common major postoperative complication. The incidence of major postoperative complications did not differ between procedures (P = .1239), although, when combined, epiglottopexy procedures (30/55) had a higher incidence of complications than epiglottectomy procedures (4/16; P = .048). Thirty (60%) dogs were alive at a median of 928 days (range, 114-2805), 8 (16%) were lost to follow-up after 411 days (range, 43-1158), and 12 (24%) were dead/euthanized after 301.5 days (range, 3-1212). Median survival time was not reached after a median of 716 days. CONCLUSION: Although intraoperative complications were uncommon, major postoperative complications were common, especially after epiglottopexy procedures. CLINICAL SIGNIFICANCE: Although surgical treatment of ER is associated with a high rate of major postoperative complications, especially epiglottopexy procedures, long-term survival can be achieved.

No environmental context-dependent effect, but interference, of physical activity on object location memory.

Research on context-dependent memory has addressed many external and internal types of contexts. However, whether the physical activity engaged in at the time of encoding and recall can act as an environmental context cue has been systematically investigated only in one study. The purpose of the present study was to replicate this; furthermore, given the effect of physical activity/effort on the way space is represented, we sought to extend the findings to object location memory. Using a 1-list paradigm (Experiment 1) and a 2-list paradigm (Experiment 2), participants had to learn the locations of objects on a grid and then recall them, while standing or walking on a health walker. No evidence of activity context effects was found. However, an interference effect of the motor task on location memory was detected, such that participants' performance was worse when walking, compared to standing, at encoding (Experiment 2) or recall (Experiment 1). Results are discussed based on the outshining hypothesis and the possible link between motor task and object location memory.

Paediatric Ewing-like sarcoma arising from the cranium - a unique diagnostic challenge.

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Predictive factors for colonic resection in patients less than 49 years with symptomatic diverticular disease.

BACKGROUND: Diverticular disease is a condition strongly associated with low-fiber intake and obesity. There have been reports of an increasing incidence in younger individuals ranging from 12% to 21% of all cases. The aim of this study was to evaluate the management of complicated diverticular disease in patients less than 49 years and attempt to identify factors predictive of a more virulent course. METHODS: An analysis of a prospectively updated database of all patients admitted with a primary diagnosis of acute diverticulitis from 2005 to 2013 was performed. Data collected included age, length of stay, inflammatory markers on admission, use of computed tomography (CT), and Hinchey Classification. SPSS version 22 was used for statistical analysis, and a P value of .05 or less was considered significant. RESULTS: A total of 120 (54 female and 66 male) patients less than 49 (28 to 49, 42.1) years were noted to have a diagnosis of acute diverticulitis. Twelve patients (10%) required colonic resection for complicated diverticulitis. Histological evaluation revealed 5 cases of stricture, 2 obstruction, and 5 perforations. On multivariate analysis, predictors of operative intervention and/or colonic resection included, (hazard ratio [95% confidence interval]) patients aged 40 to 49 years (.92 [.9 to .95]) and elevated C-reactive protein on index admission (1.4 [1.32 to 1.54]). Females were less likely to undergo colonic resection compared with males (1.18 [1.15 to 1.2]). Median length of stay was 4 days (1 to 48) for patients managed nonoperatively and 13 days (5 to 27) for those who underwent surgery. CONCLUSIONS: Most younger patients with acute diverticulitis can be treated successfully by conservative means. However, a proportion of patients require aggressive surgical management.

Lateral caudal axial pattern flap in 13 dogs.

OBJECTIVE: To describe the frequency and extent of complications associated with lateral caudal axial pattern flaps used to cover large traumatic or excision skin defects on the dorsum, gluteal, and perineal region in 13 dogs. STUDY DESIGN: Case series. ANIMALS: Thirteen client-owned dogs. METHODS: Medical records from 8 institutions were reviewed for dogs treated with a lateral caudal axial pattern flap, including cases in which the procedure was combined with other reconstructive techniques. The flap length relative to the tail length, location of tail skin incision, size and cause of the defect, and short- and long-term complications were recorded. RESULTS: Thirteen dogs were included, 11 with tumors and 2 with traumatic skin loss. The mean estimated length of the flap relative to tail length was 51% (range 33-70%). Four dogs had wound complications. This included 2 dogs with minor postoperative wound complications (mild distal dehiscence) that did not require surgical revision and 2 dogs with major complications that required surgical revision. Two of these 4 dogs had distal flap necrosis, one was revised surgically and one was managed conservatively. In these 2 dogs, the flap length was estimated as 80% and 65% of the tail length, respectively. At 30 days, flaps in all dogs were completely healed. No long-term complications were recorded in any dog. For some dogs, the reconstruction was not obvious, with only the change in hair direction and color noticeable. CONCLUSION: Lateral caudal axial pattern flap is a reconstructive option for gluteal, dorsal, and perineal skin defects in dogs. Distal flap necrosis and dehiscence due to wound infection occurred in 4 dogs that required additional wound care but not always surgical revision.

Individual differences in recognising involuntary autobiographical memories: impact on the reporting of abstract cues.

This study examined individual differences in the ability to recognise involuntary autobiographical memories. We hypothesised that individuals may not always recognise involuntary memories which are cued by abstract experiences (e.g., thoughts or language), while they are better able to recognise those which are cued by concrete sensory/perpetual experiences. We hypothesised that individuals without formal training in psychology would be more prone to these recognition failures than individuals with training in psychology. We tested the hypothesis by comparing the results of general first-year undergraduate students, graduate students in psychology and graduates students in other disciplines after each had participated in a two-week diary study of their naturally occurring involuntary memories. The results showed undergraduate participants and non-psychology graduate participants reporting fewer involuntary memories being triggered by abstract cues than the graduate psychology participants, while the groups did not differ in the report of memories triggered by sensory/perpetual cues. The implications of the findings are discussed.

Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies.

Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatment-related toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental pre-clinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase II trials that will be summarized in this review.

Closed suction drainage for treatment of septic peritonitis of confirmed gastrointestinal origin in 20 dogs.

OBJECTIVE: To determine survival rate in dogs with septic peritonitis of confirmed gastrointestinal origin treated with closed suction drainage. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 20) with septic peritonitis. METHODS: Medical records (2007-2010) of dogs with septic peritonitis of confirmed gastrointestinal origin treated by closed suction drainage were reviewed. Information on signalment, clinicopathologic abnormalities, underlying cause, surgical procedure performed, postoperative management, complications, and outcome was obtained. RESULTS: Dehiscence of a previous anastomosis was the most common source of contamination (80%). Drains remained in place, collecting fluid produced within the abdomen, for a median of 6 days (range, 2-11 days). Eighteen dogs received nutritional support, and 14 received plasma transfusions. Seventeen dogs (85%) survived to discharge. CONCLUSIONS: Closed suction drainage together with resolution of the underlying cause of peritonitis and appropriate postoperative management is an effective technique for treatment of septic peritonitis of confirmed gastrointestinal origin in dogs.

Involuntary memory chains: what do they tell us about autobiographical memory organisation?

Involuntary memory chains are spontaneous recollections of the past that occur as a sequence of associated memories. This memory phenomenon has provided some insights into the nature of associations in autobiographical memory. For example, it has shown that conceptually associated memories (memories sharing similar content, such as the same people or themes) are more prevalent than general-event associated memories (memories from the same extended event period, such as a trip). This finding has suggested that conceptual associations are a central organisational principle in the autobiographical memory system. This study used involuntary memories chains to gain additional insights into the associative structure of autobiographical memory. Among the main results, we found that general-event associations have higher rates of forgetting than conceptual associations, and in long memory chains (i.e., those with more than two memories) conceptually associated memories were more likely to activate memories in their associative class, whereas general-event associated memories were less likely to activate memories in their associative class. We interpret the results as further evidence that conceptual associations are a major organising principle in the autobiographical memory system, and attempt to explain why general-event associations have shorter lifespans than conceptual associations.

Spectrum of all-terrain vehicle injuries in adults: A case series and review of the literature.

INTRODUCTION: Serious injury secondary to all terrain vehicle usage has been widely reported since the 1970s. All-terrain vehicles (ATV) or 'quad bikes' are four wheeled vehicles used for agricultural work, recreation and adventure sport. Data collected in the U.S. indicates that ATV related injury and fatality is increasing annually. PRESENTATION OF CASES: This case series describes 3 cases of significant ATV related trauma in adults presenting to one regional hospital in the West of Ireland over a 12month period. DISCUSSION: Epidemiology, mechanisms of injury, spectrum of injury in adults and preventative measures to reduce the number of ATV related injuries and fatalities are discussed here with a review of the literature. CONCLUSION: A paucity of research outside of North America is highlighted by this case series. Mandatory reporting of ATV related injury, educational, training and legislative measures are suggested as injury prevention strategies.

Caudal mediastinal paraesophageal abscesses in 7 dogs.

OBJECTIVE: To report clinical, imaging, and surgical findings associated with caudal mediastinal paraesophageal abscesses (CMPA) in dogs and outcome after surgical treatment. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 7) with CMPA. METHODS: Medical records (April 2005-January 2010) were reviewed for dogs with CMPA treated surgically. Retrieved data were signalment, history, clinical findings, diagnostic investigations, surgical findings, surgical procedures performed, and postoperative recovery. Long-term follow-up information was obtained by telephone questionnaire of owners and referring veterinarians. RESULTS: Median sternotomy (5 dogs) or lateral thoracotomy (2 dogs) was used for access to CMPA, which were drained and partially debrided surgically. In 5 dogs, omentalization of the abscess cavity was performed through a diaphragmatic incision. Foreign material was not identified within any abscess. All dogs were discharged from the hospital and had full recovery. CONCLUSIONS: CMPA should be suspected when there is regurgitation and pyrexia associated with a mass or enlargement in the caudal mediastinum. CMPA appears to have a good prognosis after aggressive surgical therapy.

Proteomics analyses of human optic nerve head astrocytes following biomechanical strain.

We investigate the role of glial cell activation in the human optic nerve caused by raised intraocular pressure, and their potential role in the development of glaucomatous optic neuropathy. To do this we present a proteomics study of the response of cultured, optic nerve head astrocytes to biomechanical strain, the magnitude and mode of strain based on previously published quantitative models. In this case, astrocytes were subjected to 3 and 12% stretches for either 2 h or 24 h. Proteomic methods included nano-liquid chromatography, tandem mass spectrometry, and iTRAQ labeling. Using controls for both stretch and time, a six-plex iTRAQ liquid chromatography- tandem MS (LC/MS/MS) experiment yielded 573 proteins discovered at a 95% confidence limit. The pathways included transforming growth factor ß1, tumor necrosis factor, caspase 3, and tumor protein p53, which have all been implicated in the activation of astrocytes and are believed to play a role in the development of glaucomatous optic neuropathy. Confirmation of the iTRAQ analysis was performed by Western blotting of various proteins of interest including ANXA 4, GOLGA2, and αB-Crystallin.

Quasistationary analysis of the contact process on annealed scale-free networks.

We present an analysis of the quasistationary (QS) state of the contact process (CP) on annealed scale-free networks using a mapping of the CP dynamics in a one-step process and analyzing numerically and analytically the corresponding master equation. The relevant QS quantities determined via the master equation exhibit an excellent agreement with direct QS stochastic simulations of the CP. The high accuracy of the resulting data allows a probe of the strong corrections to scaling present in both the critical and supercritical regions, corrections that mask the correct finite-size scaling obtained analytically by applying an exact heterogeneous mean-field approach. Our results represent a promising starting point for a deeper understanding of the contact process and absorbing phase transitions on real (quenched) complex networks.

Modern management of pyogenic hepatic abscess: a case series and review of the literature.

BACKGROUND: Pyogenic hepatic abscesses are relatively rare, though untreated are uniformly fatal. A recent paradigm shift in the management of liver abscesses, facilitated by advances in diagnostic and interventional radiology, has decreased mortality rates. The aim of this study was to review our experience in managing pyogenic liver abscess, review the literature in this field, and propose guidelines to aid in the current management of this complex disease. METHODS: Demographic and clinical details of all patients admitted to a single institution with liver abscess over a 5 year period were reviewed. Clinical presentation, aetiology, diagnostic work-up, treatment, morbidity and mortality data were collated. RESULTS: Over a 5 year period 11 patients presented to a single institution with pyogenic hepatic abscess (55% males, mean age 60.3 years). Common clinical features at presentation were non-specific constitutional symptoms and signs. Aetiology was predominantly gallstones (45%) or diverticular disease (27%). In addition to empiric antimicrobial therapy, all patients underwent radiologically guided percutaneous drainage of the liver abscess at diagnosis and only 2 patients required surgical intervention, including one 16-year old female who underwent hemi-hepatectomy for a complex and rare Actinomycotic abscess. There were no mortalities after minimum follow-up of one year. CONCLUSIONS: Pyogenic liver abscesses are uncommon, and mortality has decreased over the last two decades. Antimicrobial therapy and radiological intervention form the mainstay of modern treatment. Surgical intervention should be considered for patients with large, complex, septated or multiple abscesses, underlying disease or in whom percutaneous drainage has failed.

Radiolucent wooden foreign body masquerading as a depressed skull fracture.

The following case describes a head injury in an older male patient in which a large wooden foreign body, forming a subcutaneous tract in the scalp, was mistaken for a depressed skull fracture on initial clinical assessment. This foreign body was not visualised on CT brain imaging until specialised views were used retrospectively, after surgical exploration of the scalp laceration. Appropriate radiological techniques for the detection of radiolucent foreign bodies are discussed.