Electromechanical vortex filaments during cardiac fibrillation.

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

Good Practices for the Laboratory Performance Testing of Aqueous Oral Inhaled Products (OIPs): an Assessment from the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS).

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products.

Degeneration alters the biomechanical properties and structural composition of lateral human menisci.

OBJECTIVE: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration. DESIGN: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content. RESULTS: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements. CONCLUSION: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity.

Osseointegration of titanium implants with a novel silver coating under dynamic loading.

Postoperative implant-associated infections are a severe complication in orthopaedics and trauma surgery. To address this problem, a novel implant coating was recently developed, which allows for the release of low concentrations of bactericidal silver. For an intended use on load-bearing endoprostheses, stable bone integration is required. The aim of the present study was to evaluate the biocompatibility and osseointegration of titanium implants with the novel coating in a mechanically loaded bone-defect model in sheep. Silver-coated devices were implanted into weight-bearing and non-weight-bearing tibial and femoral bone defects whereas, in the control group, uncoated titanium implants were inserted. The bony integration of the implants was assessed mechanically and histologically after 6 months. Silver concentrations were assessed in peripheral blood, liver, kidney and local draining lymph nodes as well as at the implantation site. After 6 months, shear strength at the interface and bone apposition to the implant surface were not significantly different between coated and uncoated devices. Mechanical loading reduced bony integration independently of the coating. Silver content at the implantation site was larger in the group with silver-coated implants, yet it remained below toxic levels and no cytotoxic side effects were observed. Concluding, the novel antibacterial silver coating did not negatively influence bone regeneration or implant integration under mechanically unloaded and even loaded conditions, suggesting that the silver coating might be suitable for orthopaedic load-bearing implants, including endoprostheses.

Transvaginal rectopexy using the Flex® Colorectal Drive Robotic System: a proof-of-concept approach to rectal prolapse.

BACKGROUND: The aim of this study was to demonstrate a proof-of-concept approach to rectopexy that would provide the durability of the transabdominal procedure through use of sacral rectopexy with the decreased morbidity of a perineal procedure. This was done by utilizing a transvaginal approach and developing the rectovaginal space to accommodate sacral rectopexy placement using the Flex® Colorectal Drive Robotic System by Medrobotics (Medrobotics Corp., Raynham, MA, USA). METHODS: A fresh female cadaver was acquired and placed in the high lithotomy position. The rectovaginal space was developed to accommodate the trocar of the Flex robot using blunt and sharp dissection between the posterior vaginal wall and anterior rectum. A piece of mesh was introduced into the space and using an endoscopic tacker, which was secured to the sacral promontory. The mesh was secured to the anterior rectal wall using interrupted vicryl sutures. The purse string suture was removed and the rectovaginal orifice was closed using a running vicryl suture. At the completion of the procedure, a low midline laparotomy was conducted to verify anchoring of the mesh appropriately at the sacral promontory. RESULTS: This proof-of-concept protocol is the first description of the Flex® Colorectal Drive being used successfully to perform a transvaginal rectopexy for rectal prolapse in a cadaver. This is also the first description of the Flex® Colorectal Drive robot being used transvaginally. CONCLUSIONS: This proof-of-concept approach demonstrates that transvaginal rectopexy using the Flex® Colorectal Drive is a potential surgical option to address rectal prolapse that could provide patients the durability of a transabdominal approach with the decreased morbidity of a perineal approach. While early results are promising, additional cadaveric studies are required before this procedure can be attempted in vivo.

Physician trust and depression influence adherence to factor replacement: a single-centre cross-sectional study.

INTRODUCTION: Poor adherence to factor replacement therapy among patients with haemophilia can lead to joint bleeding and eventual disability. AIM: The aim of this study was to determine patient-related characteristics associated with adherence to factor replacement in adults with haemophilia. METHODS: Adults with haemophilia were recruited to participate in this cross-sectional study. Adherence was measured using either the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)-Pro or the VERITAS-PRN questionnaire. Simple and multiple regression analyses that controlled for confounding were performed to determine the association between patient-related characteristics and adherence to factor replacement therapy. RESULTS: Of the 99 subjects enrolled, all were men; 91% had haemophilia A and 78% had severe disease. Age ranged from 18 to 62 years. Most (95%) had functional health literacy; but only 23% were numerate. Mean adherence scores were 45.6 (SD 18) and 51.0 (SD 15) for those on a prophylactic and those on an episodic regimen, respectively, with a lower score indicating better adherence. On multivariable analysis, being on any chronic medication, longer duration followed at our haemophilia treatment centre, higher physician trust and better quality of life were associated with higher adherence. A history of depression was associated with lower adherence. CONCLUSION: Two potentially modifiable characteristics, physician trust and depression, were identified as motivator and barrier to adherence to factor replacement therapy. Promoting a high level of trust between the patient and the healthcare team as well as identifying and treating depression may impact adherence to factor replacement therapy and accordingly reduce joint destruction.

Effect of 1,25(OH)2 D3 and 20(OH)D3 on interleukin-1ß-stimulated interleukin-6 and -8 production by human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Vitamin D-1,25(OH)2 D3 or 1,25D3-maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3 -20(OH)D3 or 20D3-on IL-1ß-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. MATERIAL AND METHODS: Human gingival fibroblasts were incubated ± IL-1ß, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: IL-1ß-stimulated IL-6 and IL-8 levels were both significantly inhibited (40%-60%) (P<.045) by 1,25D3, but not 20D3 (0%-15% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1ß-stimulated nuclear levels of p65 and phospho-cJun (P<.02). CONCLUSION: Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1ß stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.

Certainty and safe consequence responses provide additional information from multiple choice question assessments.

BACKGROUND: Clinicians making decisions require the ability to self-monitor and evaluate their certainty of being correct while being mindful of the potential consequences of alternative actions. For clinical students, this ability could be inferred from their responses to multiple-choice questions (MCQ) by recording their certainty in correctness and avoidance of options that are potentially unsafe. METHODS: Response certainty was assessed for fifth year medical students (n = 330) during a summative MCQ examination by having students indicate their certainty in each response they gave on the exam. Incorrect responses were classified as to their inherent level of safeness by an expert panel (response consequence). Analyses compared response certainty, response consequence across student performance groupings. RESULTS: As students' certainty in responses increased, the odds they answered correctly increased and the odds of giving unsafe answers decreased. However, from some ability groups the odds of an incorrect response being unsafe increased with high certainty. CONCLUSIONS: Certainty in, and safeness of, MCQ responses can provide additional information to the traditional measure of a number correct. In this sample, even students below standard demonstrated appropriate certainty. However, apart from those scoring lowest, student's incorrect responses were more likely to be unsafe when they expressed high certainty. These findings suggest that measures of certainty and consequence are somewhat independent of the number of correct responses to MCQs and could provide useful extra information particularly for those close to the pass-fail threshold.

Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo.

BACKGROUND: Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. OBJECTIVE: To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE < 3 kDa) on the human allergic immune response in vivo. METHODS: Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet-APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet-APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. RESULTS: Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet-APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. CONCLUSIONS: Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients.

Triggering of New Madrid seismicity by late-Pleistocene erosion.

The spatiotemporal behaviour of earthquakes within continental plate interiors is different from that at plate boundaries. At plate margins, tectonic motions quickly reload earthquake ruptures, making the location of recent earthquakes and the average time between them consistent with the faults' geological, palaeoseismic and seismic histories. In contrast, what determines the activation of a particular mid-continental fault and controls the duration of its seismic activity remains poorly understood. Here we argue that the concentration of magnitude-7 or larger earthquakes in the New Madrid seismic zone of the central United States since the end of the last ice age results from the recent, climate-controlled, erosional history of the northern Mississippi embayment. We show that the upward flexure of the lithosphere caused by unloading from river incision between 16,000 and 10,000 years ago caused a reduction of normal stresses in the upper crust sufficient to unclamp pre-existing faults close to failure equilibrium. Models indicate that fault segments that have already ruptured are unlikely to fail again soon, but stress changes from sediment unloading and previous earthquakes may eventually be sufficient to bring to failure other nearby segments that have not yet ruptured.

Distress in patients with bleeding disorders: a single institutional cross-sectional study.

INTRODUCTION: Distress may affect a patient's ability to cope with and manage disease. AIM: To report distress prevalence in adult patients with bleeding disorders and determine whether specific clinical and health characteristics, including disease severity and employment status, are associated with distress. METHODS: Patients who visited a Haemophilia Treatment Centre (HTC) between January 1st, 2012 through February 28th, 2014 and who completed a distress screen, pain screen and questionnaire were evaluated cross sectionally. Distress was measured by the National Comprehensive Cancer Network Distress Management Tool, which allowed patients to rate recent distress on a 0-10 point scale. A rating of five or more was categorized as high distress. Pain was measured by the Brief Pain Inventory Short Form, which asked patients to rate pain types on 0-10 point scales. Patients reported employment and other demographic and behavioural information on the questionnaire. Primary diagnosis, age, HIV and HCV status were abstracted from medical records. Adjusted logistic regression was used to identify distress associations. RESULTS: High distress prevalence among 152 patients with bleeding disorders was 31.6%. Unemployment, disability, greater depressive symptoms and higher pain were associated with high distress in multivariable models. Bleeding disorder diagnosis, race/ethnicity, HIV/HCV status and on-demand treatment regimen were not associated with high distress. CONCLUSION: Distress among patients with congenital bleeding disorders followed at a comprehensive HTC was high and similar to that reported among patients with cancer. Future research should determine whether distress impacts clinical outcomes in patients with bleeding disorders as demonstrated in other chronic disorders.

Simulated colonoscopy training using a low-cost physical model improves responsiveness of surgery interns.

AIM: Surgery residents are required to become proficient in colonoscopy before completing training. The aim of this study was to evaluate the responsiveness of surgery interns to simulated colonoscopy training. METHOD: Interns, defined as postgraduate year 1 residents without exposure to endoscopy, underwent training in a physical model including colonoscopy, synthetic anatomy trays with luminal tattoos and a hybrid simulator. After baseline testing and mentored training, final testing was performed using five predetermined proficiency criteria. Content-valid metrics defined by the extent of departure from clinical reality were evaluated by two blinded assessors. Responsiveness was defined as change in performance over time and assessed comparing baseline testing with nonmentored final testing. RESULTS: Twelve interns (eight male, mean age 26, 80% right-handed) performed 48 colonoscopies each over 1 year. Improvement was seen in the overall procedure time (24 min 46 s vs 20 min 54 s; P = 0.03), passing the splenic flexure (20 min 33 s vs 10 min 45 s; P = 0.007), passing the hepatic flexure (23 min 31 s vs 12 min 45 s; P = 0.003), caecal intubation time (23 min 38 s vs 13 min 26 s; P = 0.008), the duration of loss of view of the lumen (75% vs 8.3%; P = 0.023), incomplete colonoscopy (100% vs 33.3%; P = 0.042), colonoscope withdrawal < 6 min (16.7% vs 8.3%; P = 0.052). Tattoo identification time (9 min 16 s vs 12 min 25 s; P = 0.50), colon looped time (2 min 12 s vs 1 min 45 s; P = 0.50) and rate of colon perforation (8.3% vs 8.3%; P = 1) remained unchanged. Interrater reliability was 1.0 for all measures. CONCLUSION: Simulated colonoscopy training in a low-cost physical model improved the performance of surgery interns with decreased procedure time, increased rates of complete colonoscopy and appropriate scope withdrawal.

Red Blood Cell Distribution Width is Associated with Poor Clinical Outcome After Subarachnoid Hemorrhage: A Pilot Study.

INTRODUCTION: The red cell distribution width (RDW) is a biomarker strongly associated with poor outcome in inflammatory and thrombotic diseases. Subarachnoid hemorrhage (SAH) is both an inflammatory and thrombotic state in which many biomarkers have been studied. In this exploratory pilot study, we sought to determine whether RDW predicts poor outcome in patients with SAH. METHODS: Patients with moderate-to-severe SAH were prospectively enrolled in an observational study of biomarkers and outcome. CBC, ESR, high sensitivity CRP, D-dimer, and fibrinogen were obtained on post-bleed days (PBD) 1, 3, 5, 7, and 10. Poor outcome was defined as a modified Rankin score of 3-6 at 90-days. RESULTS: Of 40 patients, 5 (12.5%) died and 19 (47.5%) had a poor outcome. RDW (p = 0.046) when measured serially over the study period, was significantly higher among patients with poor outcome. Maximum RDW (OR 2.3 95% CI 1.2-3.6; p = 0.014) and maximum WBC count (OR 1.29 95% CI 1.04-1.60; p = 0.018) were associated with poor outcome. Stepwise addition of maximum ESR, CRP, D-dimer, and fibrinogen yielded a model with RDW (OR 2.54 95% CI 1.21-5.35; p = 0.014) and fibrinogen (OR 1.01 95% CI 1.002-1.01; p = 0.004) predicting outcome. With addition of age and Hunt and Hess grade, RDW, fibrinogen, and high-grade status remained significantly associated with poor outcome. Use of PBD1 RDW in lieu of maximum RDW, resulted in a similar model. CONCLUSIONS: An elevated RDW is associated with poor outcome in SAH patients. RDW may be a useful predictor of outcomes after SAH.

[Evaluation of an Intensified Dental Preventive Programme Aimed at Children with Increased Caries Risk]. / Evaluation eines zahnmedizinischen Präventionsprogramms für Kinder mit erhöhtem Kariesrisiko.

Our study investigated the effect of a selective intensive prevention (SIP) programme on dental health of pupils in comparison to a control group. While no differences were observed in respect to dental health of first graders, the DMF-T values of fourth and 6 graders participating in SIP were significantly lower. Concerning the psychometric variables only few differences were found. The fourth and 6 graders in the test group reported less dental fear than the pupils in the control group.

Bone density in haemophilia: a single institutional cross-sectional study.

Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross-sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm(-2) (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects <50 years (n = 62), after controlling for BMI, alcohol, HIV and White race, BMD decreased as radiographic joint score increased (est. ß = -0.006 mg cm(-2) ; 95% CI -0.009, -0.003; partial R(2) = 0.23). Among subjects ≥50 years (n = 26), 38% had osteoporosis (T score less than or equal to -2.5) and there was no association between BMD and arthropathy. Risk factors for low BMD in men with haemophilia <50 years include haemophilic arthropathy, low or normal BMI and HIV. Men with haemophilia over age 50 years should have routine screening for detection of osteoporosis.

Re-evaluating the role of vitamin D in the periodontium.

The importance of vitamin D in maintaining skeletal health via the regulation of calcium has long been recognized as a critical function of this secosteroid. An abundance of literature shows an association between oral bone mineral density and some measure of systemic osteoporosis and suggests that osteoporosis/low bone mass may be a risk factor for periodontal disease. Recently, nonskeletal functions of vitamin D have gained notoriety for several reasons. Many cells that are not associated with calcium homeostasis have been demonstrated to possess membrane receptors for vitamin D. These include activated T and B lymphocytes, and skin, placenta, pancreas, prostate and colon cancer cells. In addition, vitamin D "insufficiency" is a worldwide epidemic and epidemiologic evidence has linked this condition to multiple chronic health problems, including cardiovascular and autoimmune diseases, hypertension and a variety of cancers. Interestingly, there is mounting evidence connecting diminished serum levels of vitamin D with increased gingival inflammation and supporting the concept of "continual vitamin D sufficiency" in maintaining periodontal health. The ability of vitamin D to regulate both the innate and the adaptive components of the host response may play an important role in this process. This review will examine the skeletal and nonskeletal functions of vitamin D, and explore its potential role in protecting the periodontium as well as in regulating periodontal wound healing.

Surgical site infection rates: open versus hand-assisted colorectal resections.

PURPOSE: This study was performed to determine impact of open and hand-assisted colorectal resection on surgical site infection (SSI) rates. METHODS: National Surgical Quality Improvement Project data from 2006 to 2008 were supplemented with an institutional review board-approved chart review. Primary endpoint was SSI rates defined by the Centers for Disease Control National Nosocomial Infections Surveillance system and classified as superficial, deep incisional, and organ space. Inclusion criteria were elective or emergency open or hand-assisted colorectal resections. Wounds were classified as clean-contaminated, contaminated, or dirty-infected. Patients were not included if they underwent laparoscopic colorectal resection, small bowel resection, or stoma creation. RESULTS: Two hundred and forty-five consecutive patients were included over a 29-month period. One hundred and ninety-five open and 50 hand-assisted patients were comparable for gender, body mass index, ethnicity, tobacco addiction, steroid use, type of colorectal resection, operating time, and method of wound closure. Differences in ASA class, wound classification, and preexisting comorbidities resolved when 80 open and 5 hand-assisted patients who underwent emergency resections were excluded from analysis. Rate of stoma creation remained higher in open patients even after excluding emergency cases (p < 0.01). Overall SSI rates following open and hand-assisted resections were 28 and 44 %, respectively (p = 0.015). Superficial SSI rates were higher in hand-assisted patients (20 vs. 40 %, p = 0.006). Deep (2.1 vs. 4 %, p = 0.605) and organ space SSI rates (5.1 vs. 0 %, p = 0.221) did not differ. These results did not change when emergency resections were excluded: overall 28 and 44 % (p = 0.015), superficial (23 vs. 44 %, p = 0.009), deep (3.5 vs. 4.4 %, p = 0.541), and organ space (7 vs. 0 %, p = 0.066). CONCLUSION: This study seems to suggest possibly higher rates of incisional SSI in patients who underwent hand-assisted colorectal resection as compared to open. This retrospective study had, however, insufficient power to stratify by surgeon and control for risk factors by logistic regression.

The contribution of estuary-resident life histories to the return of adult Oncorhynchus kisutch.

This study evaluated estuarine habitat use, life-history composition, growth and survival of four successive broods of coho salmon Oncoryhnchus kisutch in Salmon River, Oregon, U.S.A. Subyearling and yearling O. kisutch used restored and natural estuarine wetlands, particularly in the spring and winter. Stream-reared yearling smolts spent an average of 2 weeks in the estuary growing rapidly before entering the ocean. Emergent fry also entered the estuary in the spring, and some resided in a tidal marsh throughout the summer, even as salinities increased to >20. A significant portion of the summer stream-resident population of juvenile O. kisutch migrated out of the catchment in the autumn and winter and used estuary wetlands and adjacent streams as alternative winter-rearing habitats until the spring when they entered the ocean as yearling smolts. Passive integrated transponder (PIT) tag returns and juvenile life-history reconstructions from otoliths of returning adults revealed that four juvenile life-history types contributed to the adult population. Estuarine-associated life-history strategies accounted for 20-35% of the adults returning to spawn in the four brood years, indicating that a sizable proportion of the total O. kisutch production is ignored by conventional estimates based on stream habitat capacity. Juvenile O. kisutch responses to the reconnection of previously unavailable estuarine habitats have led to greater life-history diversity in the population and reflect greater phenotypic plasticity of the species in the U.S. Pacific Northwest than previously recognized.

Physical activity and functional abilities in adult males with haemophilia: a cross-sectional survey from a single US haemophilia treatment centre.

Physical activity and functional ability are important determinants of quality of life and these metrics are affected by both haemophilia and ageing. Outside haemophilic arthropathy, risk factors leading to reduced physical activity and function in people with haemophilia (PWH) are under-explored. The purpose of this analysis was to determine risk factors for reduced physical activity and functional limitations in PWH. A secondary analysis was conducted on data indexing physical activity and functioning of 88 PWH using data originally collected as part of a cross-sectional study at a single large haemophilia treatment centre. The Framingham Physical Activities Index (PAI), the Hemophilia Activities List (HAL) and the Timed Up-and-Go Test (TUG) were the outcome measures. The World Federation of Haemophilia (WFH) orthopaedic joint score was used as a measure of arthropathy. Multiple linear regression analysis was used to assess the relationship between the outcome measures and covariates. Worsening WFH joint score was independently associated with all three outcome measures (P < 0.05). Increasing age was associated with reduced PAI and increased TUG time (P < 0.05). The HAL summary score was decreased in patients with chronic liver disease (P = 0.006). The adjusted R(2) for each model was ≤ 0.35. This study provides evidence for the relationship between arthropathy and reduced physical functioning/activity, but also highlights that much of the variation in physical functioning/activity is not explained by haemophilia-related characteristics.

Deterioration in biomechanical properties of the vagina following implantation of a high-stiffness prolapse mesh.

OBJECTIVE: To define the impact of prolapse mesh on the biomechanical properties of the vagina by comparing the prototype Gynemesh PS (Ethicon) to two new-generation lower stiffness meshes, SmartMesh (Coloplast) and UltraPro (Ethicon). DESIGN: A study employing a nonhuman primate model. SETTING: University of Pittsburgh, PA, USA. POPULATION: Forty-five parous rhesus macaques. METHODS: Meshes were implanted via sacrocolpopexy after hysterectomy and compared with sham. Because its stiffness is highly directional, UltraPro was implanted in two directions: UltraPro Perpendicular (less stiff) and UltraPro Parallel (more stiff), with the indicated direction referring to the position of the blue orientation lines relative to the longitudinal axis of the vagina. The mesh-vaginal complex (MVC) was excised in toto after 3 months. MAIN OUTCOME MEASURES: Active mechanical properties were quantified as the contractile force generated in the presence of 120 mmol/l KCl. Passive mechanical properties (a tissue's ability to resist an applied force) were measured using a multiaxial protocol. RESULTS: Vaginal contractility decreased by 80% following implantation with the Gynemesh PS (P = 0.001), 48% after SmartMesh (P = 0.001), 68% after UltraPro Parallel (P = 0.001) and was highly variable after UltraPro Perpendicular (P = 0.16). The tissue contribution to the passive mechanical behaviour of the MVC was drastically reduced for Gynemesh PS (P = 0.003), but not for SmartMesh (P = 0.9) or UltraPro independent of the direction of implantation (P = 0.68 and P = 0.66, respectively). CONCLUSIONS: Deterioration of the mechanical properties of the vagina was highest following implantation with the stiffest mesh, Gynemesh PS. Such a decrease associated with implantation of a device of increased stiffness is consistent with findings from other systems employing prostheses for support.