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With the advent of practice changes surrounding preoperative patient optimization and postoperative protocols, a marked reduction has been reported in blood transfusion rates following total hip arthroplasty (THA). Thus, the purpose of this study was to examine differences in the prevalence of preoperative anemia, thrombocytopenia, elevated international normalized ratio (INR), bleeding disorders, and pre- and postoperative blood transfusions over the last decade. From 2011 to 2018, the American College of Surgeons National Quality Improvement Program database was queried for all primary THA procedures (n = 208,796). The following continuous variables were examined using analysis of variance: preoperative hematocrit (HCT), platelet count, and INR. The following categorical variables were analyzed by chi-squared tests: anemia (HCT 2.0, bleeding disorders, preoperative transfusions, and postoperative transfusions. There were decreases in preoperative anemia (2011: 16.2%; 2018: 11.4%, p 2.0 (2011: high = 1.1%; 2018: low = 0.7%, p = 0.001), bleeding disorders (2011: high = 2.9%; 2018: low = 2.0%, p

Background Bile acid diarrhoea (BAD) can be severely debilitating and negatively affect patients’ quality of life (QoL). We carried out a multi-centre prospective study exploring QoL outcomes in patients with BAD after treatment with colesevelam. Methods Patients with or without a positive 23-seleno-25-homotaurocholic acid (SeHCAT) scan were recruited and categorised into four groups: SeHCAT negative control group (CG), idiopathic BAD, post-cholecystectomy (PC) and post-terminal ileal resection for Crohn’s disease (CD). Patients with a positive SeHCAT were treated with colesevelam and dosing was titrated to symptomatic response. Patients were reviewed at 4- and 8-weekly intervals and QoL was evaluated by EQ-5D-3L, SF-36, IBDQ-32 at each visit (where relevant). Patients with a negative SeHCAT (CG cohort) completed one set of questionnaires before being discharged from the study. Results 47 patients (BAD = 24, PC = 12, CD = 11) completed paired QoL questionnaires before and after treatment and 30 CG patients completed a baseline questionnaire. There was a significant improvement in IBDQ-32 mean scores before and after treatment in CD patients [134.6 (95%CI 112.5–156.6) and 158.4 (136.1–180.6), respectively (p = 0.007). Following treatment, BAD patients had significantly improved mean SF-36 scores in the “Role limitation due to physical health” dimension (p = 0.02) and in the overall mental component summary (p = 0.03). Prior to starting treatment, BAD patients had the lowest scores in the ‘activity’ dimension of the EQ-5D-3L (p = 0.04), which improved significantly after treatment (p = 0.002). Overall, the BAD and CD cohort showed improved mean scores with treatment in all components of the SF-36 and EQ-5D-3L, while the PC cohort showed a general decline in mean scores after treatment. 55% of patients clinically responded to treatment of which 41.7%, 58.3% and 81.8% responded from the BAD, PC and CD groups respectively. Correlations between those deemed as responders with improvements on the SF-36 and EQ-5D dimensions were not statistically significant. Conclusion Our results demonstrate improved QoL in the BAD and CD cohort with treatment. Further larger studies are recommended specifically investigating the PC cohort and whether patients may improve with newer treatments such as FXR agonists. Trial registration Ethical approval REC Ref: 16/LO/1325.

Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database. For those variants identified as significant in the two datasets, we further performed stratified analyses by smoking status and histological type and investigated their effects on gene expression and potential regulatory mechanisms. We identified three genetic variants significantly associated with lung cancer risk: rs329118 in JADE2 (P = 8.80E−09), rs2285521 in GGA2 (P = 4.43E−08), and rs198459 in MYRF (P = 1.60E−06). The combined effects of all three SNPs were more evident in lung squamous cell carcinomas (P = 1.81E−08, P = 6.21E−08, and P = 7.93E−04, respectively) than in lung adenocarcinomas and in ever smokers (P = 9.80E−05, P = 2.70E−04, and P = 2.90E−05, respectively) than in never smokers. Gene expression quantitative trait analysis suggested a role for the SNPs in regulating transcriptional expression of the corresponding target genes. In conclusion, we report that three RNA splicing-related genetic variants contribute to lung cancer susceptibility in European populations. However, additional validation is needed, and specific splicing mechanisms of the target genes underlying the observed associations also warrants further exploration.

Hip fractures are associated with poor mortality and morbidity outcomes. Controversy exists over what the preferred treatment is between sliding hips screws (SHSs) and cephalomedullary nails (CMNs) for stable intertrochanteric (IT) and basicervical (BC) hip fractures. The purpose of this study was to compare early postoperative outcomes and complications in patients treated with SHS to those treated with CMN in IT and BC hip fractures. We used the National Surgical Quality Improvement Program database to identify IT and BC hip fractures, excluding subtrochanteric hip fractures treated with a SHS and CMN for 2008 to 2016. After propensity score matching, there were 8505 patients in the SHS cohort and 8505 in the CMN cohort. Propensity score-adjusted multivariate regression models assed SHS as an independent risk factor for the following 30-day outcomes: mortality, postoperative major and minor complications, discharge disposition, readmission and reoperation, length of hospital stay (LOS), and operative time. No difference in mortality was encountered between SHS and CMN (p = 0.440). Compared to CMN, the SHS cohort had an 11.6% decreased likelihood of a minor complication (p

Early mobilization and weight-bearing have been proposed to improve hip fracture outcomes. This study aimed to compare early postoperative complications and outcomes of patients who underwent weight-bearing as tolerated (WBAT) on postoperative day one (POD1) with those that did not on: (1) 30-day mortality; (2) 30-day postoperative major and minor complications; (3) length of stay (LOS); and (4) discharge disposition after hip fracture management. The NSQIP database was used to identify 7947 hip fracture patients managed with a hemiarthroplasty and internal fixation, sliding hip screw, or cephalomedullary nail, for a total of 5845 patients were allowed to WBAT on POD1. They were compared to patients who were non-WBAT using adjusted multivariate regression models to evaluate the effect of WBAT status on the outcomes above. Among the cephalomedullary nail patients, WBAT on POD1 was associated with a decreased likelihood of mortality. In the cephalomedullary nail and sliding hip screw treatment groups, patients were less likely to experience major and minor complications if they were WBAT on POD1. WBAT patients had shorter LOS in the sliding hip screw and cephalomedullary nail treatment groups. Patients were less likely to be discharged to a non-home facility when WBAT on POD1 regardless of treatment. Early weight-bearing after surgical care of hip fracture seems to decrease morbidity and mortality; however, this effect is treatment dependent. These findings further support the need for early mobilization and rapid recovery programs in the care of hip fracture patients. Level III.

The metal foams of a titanium alloy were designed to study porosity as well as pore size and shape independently. These were manufactured using a powder metallurgy/space-holder technique that allowed a fine control of the pore size and morphology; and then characterized and tested against well-established models to predict a relationship between porosity, pore size and shape, and bulk stiffness. Among the typically used correlations, existing power-law models were found to be the best fit for the prediction of macropore morphology against compressive elastic moduli, outperforming other models such as exponential, polynomial or binomial. Other traditional models such as linear ones required of updated coefficients to become relevant to metal porous sintered macrostructures. The new coefficients reported in this study contribute toward a design tool that allows the tailoring of mechanical properties through porosity macrostructure. The results show that, for the same porosity range, pore shape and orientation have a significant effect on mechanical performance and that they can be predicted. Conversely, pore size has only a mild impact on bulk stiffness.

Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.

Fifty percent of patients develop chronic gastrointestinal (GI) symptoms following pelvic radiotherapy that adversely affect quality of life. Fewer than 20 % are referred to a gastroenterologist. We aimed to determine if structured gastroenterological evaluation is of benefit to this patient group.Sixty patients with GI symptoms at ≥ 6 months after radical pelvic radiotherapy were identified prospectively from oncology clinics in this service evaluation. Those requiring urgent investigation were excluded. Patients were assessed at baseline using patient-reported questionnaires: inflammatory bowel disease questionnaire (IBDQ), Vaizey incontinence questionnaire, and the Common Terminology Criteria for Adverse Events (CTCAE) pelvis questionnaire. Participants were referred for gastroenterological evaluation using an algorithmic approach. Further assessments were made at 3 and 6 months.Twenty men and 36 women with primary gynecological (31), urological (17), or lower GI (8) tumors were included (mean age, 58.5 years). Median time from radiotherapy to baseline assessment was 3.0 years. Multiple GI symptoms were reported (median, 8; range, 4-16) including frequency, urgency, loose stool, fecal incontinence, flatulence, bloating/distension, and rectal bleeding. Common diagnoses included radiation proctopathy, bile acid malabsorption, diverticulosis, and colonic polyps. Statistically significant improvements in all questionnaire scores between baseline and 6 months were found: IBDQ (p = 0.014), Vaizey (p0.0005), and CTCAE rectum-bowel subset (p = 0.001).Gastroenterological evaluation identifies significant, potentially treatable diagnoses in patients who develop chronic GI symptoms following pelvic radiotherapy. Some findings are incidental and unrelated to previous cancer treatment. Radiation-induced GI symptoms have historically been considered "untreatable." We report the first data to show that structured gastroenterological assessment has the potential to improve outcome by identifying diagnoses and facilitating focused treatment.

There is considerable interest in whether non-nutritive sweeteners are sensed in the gastrointestinal tract to modulate appetitive or absorptive responses to ingested carbohydrate. We determined the effect of a panel of non-nutritive sweeteners, aspartame, saccharin and acesulfame-K, delivered in doses that would be consumed in normal usage. Each was given in combination with glucose, assessing their effect on glycemic responses and appetite in ten healthy human subjects. There was no additional effect of aspartame or saccharin on the blood glucose response to oral glucose at any time point, although acesulfame-K exerted a small effect. However, none had an effect on perceptions of hunger or fullness. We conclude that there is no consistent evidence that non-nutrient sweeteners, when acutely consumed with glucose in dietetically relevant doses, have a class effect in modulating blood glucose in healthy human subjects. However, acesulfame-K may require further exploration.

Although there is a substantial body of literature on the physical and psychosexual consequences of stroke, there is a paucity of empirical studies on the experiences of rehabilitation professionals in addressing sexuality issues with patients during the rehabilitation process. This is the first small-scale pilot study in Northern Ireland, informed by a comprehensive literature review, which explores the experiences of health and social care professionals in addressing sexuality issues with patients and their perceptions of the training they require in this area of stroke rehabilitation. Questionnaire survey data were collected from community and hospital based stroke professionals in a Health and Social Services Trust in Northern Ireland. The study groups comprised nurses, doctors, physiotherapists, occupational therapists, speech and language therapists and social workers. The findings revealed that although the majority of staff had been asked for advice on sexuality issues during rehabilitation, most of them had received no training in this aspect of stroke rehabilitation since joining stroke services. The findings suggest that all rehabilitation professionals need to become more knowledgeable about sexuality issues in stroke care and could benefit from further education and training in comprehensive sexual health care.

PURPOSE: To assess the effect of pupil dilation on vision and driving ability. METHODS: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy. Tests of basic visual function included high- and low-contrast visual acuity (HCVA and LCVA), Pelli-Robson contrast threshold (CT) and Goldmann perimetry (FIELDS). Useful Field of View (UFOV--a test of visual attention) was also undertaken. The mean differences in the pre- and post-dilatation measurements were tested for statistical significance at the 95% level using one-tail paired t-tests. RESULTS: Pupillary dilation resulted in a statistically significant deterioration in CT and HCVA only. Five of 12 drivers also exhibited deterioration in LCVA, CT and RT. Little evidence emerged for deterioration in FIELDS and UFOV. Also, 7 of 12 drivers appeared to adjust their driving behaviour by reducing their speed on the driving simulator, leading to improved steering accuracy. CONCLUSIONS: Pupillary dilation may lead to a decrease in vision and daylight driving performance in young people. A larger study, including a broader spectrum of subjects, is warranted before guidelines can be recommended. Language: en

Background Genetic susceptibility to colonic inflammation is poorly defined at the gene level. Although Genome Wide Association studies (GWAS) have identified loci in the human genome which confer susceptibility to Inflammatory Bowel Disease (Crohn’s and Ulcerative Colitis), it is not clear if precise loci exist which confer susceptibility to inflammation at specific locations within the gut e.g. small versus large intestine. Susceptibility loci for colitis in particular have been defined in the mouse, although specific candidate genes have not been identified to date. We have previously shown that infection with Trichuris muris (T. muris) induces chronic colitis in susceptible mouse strains with clinical, histological, and immunological homology to human colonic Crohn’s disease. We performed an integrative analysis of colitis susceptibility, using an F2 inter-cross of resistant (BALB/c) and susceptible (AKR) mice following T. muris infection. Quantitative Trait Loci (QTL), polymorphic and expression data were analysed alongside in silico workflow analyses to discover novel candidate genes central to the development and biology of chronic colitis. Results 7 autosomal QTL regions were associated with the establishment of chronic colitis following infection. 144 QTL genes had parental strain SNPs and significant gene expression changes in chronic colitis (expression fold-change ≥ +/-1.4). The T. muris QTL on chromosome 3 (Tm3) mapped to published QTL in 3 unrelated experimental models of colitis and contained 33 significantly transcribed polymorphic genes. Phenotypic pathway analysis, text mining and time-course qPCR replication highlighted several potential cis-QTL candidate genes in colitis susceptibility, including FcgR1, Ptpn22, RORc, and Vav3. Conclusion Genetic susceptibility to induced colonic mucosal inflammation in the mouse is conserved at Tm3 and overlays Cdcs1.1. Genes central to the maintenance of intestinal homeostasis reside within this locus, implicating several candidates in susceptibility to colonic inflammation. Combined methodology incorporating genetic, transcriptional and pathway data allowed identification of biologically relevant candidate genes, with Vav3 newly implicated as a colitis susceptibility gene of functional relevance.

It is shown how to add dissipation to the “resonant” nonlinear oscillators studied by Ford and Lunsford in such a way that the system remains on the energy surface. In the dissipative system, the energy surface is stable in some directions and neutrally stable in other directions. The dissipative oscillators are special cases of the general type investigated by Sherman and McLaughlin. The connection between resonant conservative nonlinear oscillators and dissipative oscillators may make it easier to extend the theorem of Arnol'd to dissipative systems.

A parametrically forced pendulum is studied numerically both with and without friction. In both cases, period-doubling sequences of bifurcation are found. In the dissipative case, the period-doubling sequence leads to strange attractors, while in the conservative case, the sequence is responsible for the destruction of stable zones.

A model of interacting normal modes in a nonlinear, dissipative system is constructed in order to analyze speculations by Ruelle and Takens. The first bifurcation leads to a periodic state. The second bifurcation leads to phaselocking, if the first mode is sufficiently energetic. A third bifurcation leads to stochastic behavior. Possible relevance of these phenomena for physical systems is discussed.

Recent reports have questioned the accuracy of transcutaneous measurements of oxygen tension (TcPO2), especially in older infants. We therefore validated TcPO2 values as well as pulse oximeter measurements of oxygen saturation (TcSO2) by comparing them with arterial blood in infants undergoing elective cardiac catheterization. A Litton Oxymonitor was used to measure TcPO2 and TcSO2 was monitored with a Nellcor Pulse Oximeter. Eight infants, aged from 7-61 weeks (mean 35.4), were studied. All were hemodynamically stable and normothermic. Nine simultaneous measurements were made of arterial and transcutaneous PO2, as well as SO2. The results are shown in the Table. The mean arterial-transcutaneous PO2 difference was 17.3 mmHg, while O2 saturation difference was 5.1%. Age did not affect either the arterial-transcutaneous difference in PO2 (r = -0.32), or O2 saturation (r = 0.11). However, a significant correlation existed between arterial-transcutaneous PO2 difference and skin fold thickness (r = 0.80, p