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Cementless total hip arthroplasty (THA) femoral stems are the most commonly selected prostheses in the United States. Optimal stem geometry remains controversial with excellent survivorship reported for many designs. We compared cause-specific stem revision of single-wedge versus double-wedge designs from a multicenter US cohort. Data from an integrated healthcare network's total joint replacement registry were used to conduct a cohort study. Primary elective cementless THAs were identified (2001 to 2018). Implant exposure groups were classified by design geometry using the system proposed by Khanuja et al. Type 1 single-wedge (n = 11,082) and type 2 double-wedge (n = 32,380) designs were compared, and other design types were excluded; the final study cohort comprised 43,462 THAs. Cause-specific multivariable Cox regressions were used to evaluate risk for revision due to infection or aseptic reasons, including loosening, instability, periprosthetic fracture, or other reasons. After adjustment for covariates, a higher aseptic revision risk was observed for type 1 when compared to type 2 designs (hazard ratio = 1.91, 95% confidence interval = 1.33-2.75). When looking at specific revision reasons, revision for aseptic loosening (hazard ratio = 3.46, 95% confidence interval = 2.24-5.34) was higher for type 1 versus type 2 designs. No differences were found for septic revision, instability, periprosthetic fracture, or revisions for other reasons. Type 1 single-wedge designs were found to have a higher risk of revision due to aseptic loosening relative to type 2 double-wedge designs. Femoral stem geometry should be considered when selecting a cementless femoral implant. Level III. [ABSTRACT FROM AUTHOR]

Background: Direct current cardioversion is a common management option for termination of tachydysrhythmias, including atrial fibrillation and atrial flutter. It is generally safe and effective with infrequent reporting of side effects. Pulmonary edema is a rare complication with reported incidence of 1-3% and mortality of 18%. Our literature search did not reveal any reported cases of postcardioversion pulmonary edema in the emergency medicine literature.Case Report: We report a case of an 80-year-old woman with a history of atypical atrial flutter on warfarin, paroxysmal atrial fibrillation, and rheumatic mitral valve disease who presented with shortness of breath 12 h after transesophageal echocardiography and subsequent direct current cardioversion with reversion to sinus rhythm. She was found to be in acute pulmonary edema. She was placed on noninvasive ventilation and diuresis with eventual symptom resolution. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Postcardioversion pulmonary edema is a rare complication that may occur after reversion to sinus rhythm. Emergency physicians should be cognizant of patients, especially those with underlying structural heart disease, who present with dyspnea after a recent cardioversion procedure or after cardioversion in the emergency department. Patients cardioverted in the emergency department may be observed for around 3 h and counseled on the development of respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: Epidural injections are routinely used for management of radicular pain and are prevalent nonsurgical interventions for chronic low back pain. Pneumocephalus is a rare complication that may occur as a result of inadvertent dural puncture with an epidural needle. Pneumocephalus-induced cranial nerve deficit is also rare, with only a few reported cases.Case Report: We report a case of a 61-year-old woman with a chief complaint of diplopia after she underwent epidural injection for chronic lumbar pain. Her examination was remarkable for a partial right oculomotor nerve palsy. We obtained a computed tomography brain scan, which revealed pneumocephalus. She was managed conservatively and reported complete symptom resolution after 2 weeks. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pneumocephalus is an uncommon complication of epidural spinal injections. Emergency physicians should include this on the differential for a patient presenting with cranial nerve deficit after this procedure. [ABSTRACT FROM AUTHOR]

Effective urban planning depends on knowing homebuyers' preferences for neighbourhood features that provide different amenities, such as managed parks and trees. As the expansion of tropical urban areas into biodiversity hotspots is predicted to more than double by 2030, knowing homebuyers utility from different vegetation types can contribute to global biodiversity conservation strategies. We used the hedonic pricing method to estimate the economic value of managed, spontaneous and high conservation value vegetation to Singapore public housing using a mixed effects model. On average vegetation had positive effects on property selling price, accounting for 3% of the average property's value, or a total of S$179 million for all public housing apartments sold over 13 months. These effects were almost entirely driven by managed vegetation, which had positive marginal effects on price for 98.1% of properties. The estimated marginal effects of high conservation value vegetation were mostly negative (90.5%% properties), but positive for properties without much managed vegetation nearby. The estimated marginal effects of spontaneous vegetation were mixed and mostly small. To reconcile the goals of protecting high conservation value vegetation and maximising homeowner utility, new public housing developments should contain more managed vegetation but be away from high conservation value vegetation. [ABSTRACT FROM AUTHOR]

Objectives To reduce the incidence of urinary tract infection, Surgical Care Improvement Project 9 mandates the removal of urinary catheters within 48 hours postoperatively. In patients with thoracic epidural anesthesia, we sought to determine the rate of catheter reinsertion, the complications of reinsertion, and the factors associated with reinsertion. Methods We conducted a prospective observational study of consecutive patients undergoing major pulmonary or esophageal resection with thoracic epidural analgesia over a 2-year period. As per Surgical Care Improvement Project 9, all urinary catheters were removed within 48 hours postoperatively. Excluded were patients with chronic indwelling catheter, patients with urostomy, and patients requiring continued strict urine output monitoring. Multivariable logistic regression analysis was used to identify independent risk factors for urinary catheter reinsertion. Results Thirteen patients met exclusion criteria. Of the 275 patients evaluated, 60 (21.8%) required reinsertion of urinary catheter. There was no difference in the urinary tract infection rate between patients requiring reinsertion (1/60 [1.7%]) versus patients not requiring reinsertion (1/215 [0.5%], P = .389). Urethral trauma during reinsertion was seen in 1 of 60 patients (1.7%). After reinsertion, discharge with urinary catheter was required in 4 of 60 patients (6.7%). Multivariable logistic regression analysis found esophagectomy, lower body mass index, and benign prostatic hypertrophy to be independent risk factors associated with catheter reinsertion after early removal in the presence of thoracic epidural analgesia. Conclusions When applying Surgical Care Improvement Project 9 to patients undergoing thoracic procedures with thoracic epidural analgesia, consideration to delayed removal of urinary catheter may be warranted in patients with multiple risk factors for reinsertion. [ABSTRACT FROM AUTHOR]

Nitrate concentration in most aquifers in arid and semi-arid areas has increased in the past several decades as a result of human activities. Under the predominantly oxic conditions of these aquifers, denitrification is inhibited, allowing nitrate, a soluble and stable form of nitrogen (N), to accumulate. Because of its close association with municipal and agricultural wastes, nitrate is commonly used as an indicator of anthropogenic contamination. Aquifers affected by agricultural waste may contain salts from irrigation returns and herbicides in addition to nitrates. Preventing leakage from soil to deeper parts of the aquifer is thus a priority in the sustainable management of aquifers in arid and semiarid areas. Studies report a wide range of nitrate concentrations distributed non-uniformly within the aquifer, with roughly 40% and 20% of sampled wells exceeding 50 mg/L nitrate in shallow and deep parts of the aquifer respectively. In aquifers at risk of becoming contaminated, nitrate isotopes (δ 15 N, δ 18 O, Δ 17 O) can be used to identify the source of nitrogen as mineral or organic fertilizer, sewage, or atmospheric deposition. A variety of mathematical models (crop, hydrological, geochemical, or a combination of them) have been successful in identifying best practices that minimize N leakage without negatively affecting crop yield. In addition, field research in crop management, e.g., conservation agriculture, has yielded promising results in determining the adequate dosage and time of application of fertilizers to reduce N losses. Examples of key dryland aquifers impacted by nitrate are discussed, and some of the most pressing challenges to achieve sustainability are presented. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in more than half of patients after their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence.Study Design: A cohort of patients with Crohn's disease who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at 8 loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariable survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively.Results: One hundred and ninety-one patients with Crohn's disease and 11.2 years mean postoperative follow-up were included. Forty-six percent experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male sex (p = 0.05) and shortened time to first intestinal operation (5.0 vs 7.3 years; p = 0.03); inflammatory disease behavior was associated with a lower chance of repeat operation (p < 0.01). Of the loci assessed on multivariable analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence (hazard ratio 1.54; 95% CI 1.00 to 2.36; p < 0.05).Conclusions: We identify BACH2 as a susceptibility locus for postoperative recurrence of Crohn's disease in our cohort. BACH2 is critical in the differentiation and function of T cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in postoperative Crohn's disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process. [ABSTRACT FROM AUTHOR]

Background: Matt and polished femoral stems have been historically grouped together in registry assessment of the outcome of cemented femoral stems in total hip arthroplasty. This is despite differences in the mode of fixation and biomechanics of loading. The aims of this study are to compare the survivorship of polished tapered stems with matt finished cemented stems.Methods: Data on primary total hip arthroplasty undertaken for a diagnosis of osteoarthritis from September 1999 to December 2014 were included from a National Joint Registry. Revision rates of the 2 different types of femoral components were compared.Results: There were 96,315 cemented femoral stems included, of which 82,972 were polished tapered and 13,343 matt finish. The cumulative percent revision at 14 years of polished stems was 3.6% (3.0-4.2) compared to 4.9% (4.1-5.7) for matt finish stems. Polished tapered stems had a significantly lower revision rate of femoral revision (hazard ratio 0.56, P < .001). This difference is evident in patients aged <75, and becomes apparent in the mid-term and continues to increase with time. Aseptic loosening accounts for 75% of revisions of matt finish stems compared to 20% for polished tapered stems.Conclusion: Although both polished and matt finish stems have excellent early to mid-term results, the long-term survivorship of polished stems is significantly better, with aseptic loosening becoming an issue with matt finish stems. In the future reports of cement fixation for femoral stems may benefit from separate analysis of polished and matt finish. [ABSTRACT FROM AUTHOR]

Background Parenteral prostacyclin analogs that target the prostacyclin pathway have been used to treat pulmonary arterial hypertension (PAH) since the 1990s. Abrupt discontinuation of parenteral prostacyclin analogs can be associated with acute deterioration of PAH. Less is known about temporary interruption of oral therapies that target the prostacyclin pathway, such as selexipag. Methods We evaluated the frequency, duration, reasons, and consequences of temporary selexipag interruptions among PAH patients enrolled in the Prostacyclin (PGI 2 ) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study. In GRIPHON, patients were randomized to selexipag or placebo and titrated to an individualized highest tolerated dose (200 to 1,600 µg twice daily) over 12 weeks, after which patients entered the maintenance phase. Treatment interruptions were allowed; if the interruption was < 3 days, treatment was restarted at the previous highest tolerated dose; if the interruption was ≥ 3 days, retitration from 200 µg twice daily was required. Descriptive analyses were performed. Results At least 1 treatment interruption occurred in 111 of 574 patients (19.3%) in the selexipag group and in 58 of 582 (10.0%) in the placebo group. Baseline characteristics were similar between patients with and without an interruption. Of the 111 patients in whom selexipag was temporarily interrupted, 94 (85%) were receiving background PAH therapy. Adverse events were the most common reason for selexipag interruption. Selexipag interruptions and reinstitution of treatment were well tolerated. There were no episodes of acute deterioration during treatment interruption. Conclusions Based on observations from GRIPHON, selexipag interruptions can be expected in clinical practice. However, temporarily interrupting selexipag was well tolerated and manageable. [ABSTRACT FROM AUTHOR]

We define pointfree pointwise convergence, and use it to define the Baire functions on a locale. The main result is that the Baire functions on a locale coincide with the continuous functions on its P -locale coreflection. Furthermore, we show that the Baire functions on a locale constitute the epicompletion of the continuous functions in the relevant category. The relevant category is T , the category of truncated archimedean ℓ -groups, hereafter nicknamed truncs. T is closely related to the famous category W of unital archimedean ℓ -groups. The universal objects in T are of the form R 0 L , the trunc of real-valued locale maps L → R which vanish at the designated point of a pointed locale L . We provide an intuitive definition of pointwise convergence in R 0 L which extends the classical definition, and show that it has a number of nice properties: all homomorphisms and operations of T are pointwise continuous, and a pointwise dense extension is a trunc epimorphism. Conversely, we show that every epic extension G → H has an epic extension H → K such that G is pointwise dense in K . We show that the rich theory of epimorphisms in W carries over to T with only minor modification. In particular, the epicomplete truncs comprise a full monoreflective subcategory, and are characterized as those objects of the form R 0 P for a P -locale P . In light of these facts, a reformulation of the last clause of the preceding paragraph is that any trunc is pointwise dense in any epicompletion. And a trunc is epicomplete iff it is pointwise complete, i.e., has no proper extension in which it is pointwise dense. Finally, for a given pointed locale L , we define the functions of Baire class α on L in the classical fashion. A function is Baire class 0 if it lies in R 0 L , and of Baire class β if it is the pointwise limit of a sequence of functions of Baire class α < β . A Baire function on L is a function of Baire class α for some α . Our results can be summarized as follows. Theorem For a pointed locale L with P-locale coreflection P ⁎ L → L , the Baire functions on L are precisely the continuous functions on P ⁎ L , i.e., those of R 0 P ⁎ L . Theorem The embedding R 0 L → R 0 P ⁎ L is the functorial epicompletion in T . [ABSTRACT FROM AUTHOR]

Mutations in splicing factor genes ( SF3B1 , SRSF2 , U2AF1 and ZRSR2 ) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology. These findings have led to the development of therapeutic strategies using splicing-modulating agents and rapid progress is being made in this field. Splicing inhibitors are promising agents that exploit the preferential sensitivity of splicing factor-mutant cells to these compounds. Here, we review the known target genes associated with splicing factor mutations in MDS, and discuss the potential of splicing-modulating therapies for these disorders. [ABSTRACT FROM AUTHOR]

Study Objective: To examine whether a robotic surgical platform can complement the fine motor skills of the nondominant hand, compensating for the innate difference in dexterity between surgeon's hands, thereby conferring virtual ambidexterity.Design: Crossover intervention study (Canadian Task Force classification II-1).Setting: Centers for medical simulation in 2 tertiary care hospitals of Harvard Medical School.Participants: Three groups of subjects were included: (1) surgical novices (medical graduates with no robotic/laparoscopic experience); (2) surgeons in training (postgraduate year 3-4 residents and fellows with intermediate robotic and laparoscopic experience); and (3) advanced surgeons (attending surgeons with extensive robotic and laparoscopic experience).Interventions: Each study group completed 3 dry laboratory exercises based on exercises included in the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Each exercise was completed 4 times: using the dominant and nondominant hands, on a standard laparoscopic FLS box trainer, and in a robotic dry laboratory setup. Participants were randomized to the handedness and setting order in which they tackled the tasks.Measurements and Main Results: Performance was primarily measured as time to completion, with adjustments based on errors. Means of performance for the dominant versus nondominant hand for each task were calculated and compared using repeated-measures analysis of variance. A total of 36 subjects were enrolled (12 per group). In the laparoscopic setting, the mean overall time to completion of all 3 tasks with the dominant hand differed significantly from that with the nondominant hand (439.4 seconds vs 568.4 seconds; p = .0008). The between-hand performance difference was nullified with the robotic system (374.4 seconds vs 399.7 seconds; p = .48). The evaluation of performance for each individual task also revealed a statistically significant disparate performance between hands for all 3 tasks when the laparoscopic approach was used (p = .003, .02, and .01, respectively); however, no between-hand difference was observed when the tasks were performed robotically. On analysis across the 3 surgeon experience groups, the performance advantage of robotic technology remained significant for the surgical novice and intermediate-level experience groups.Conclusion: Robot-assisted laparoscopy may eliminate the operative handedness observed in conventional laparoscopy, allowing for virtual ambidexterity. This ergonomic advantage is particularly evident in surgical trainees. Virtual ambidexterity may represent an additional aspect of surgical robotics that facilitates mastery of minimally invasive skills. [ABSTRACT FROM AUTHOR]

The reduction potential of Fe(II)-Fe(III) (oxyhydr)oxide systems provides an important control on the biogeochemical cycling of redox-sensitive elements such as carbon and nitrogen as well as trace metals and organic contaminants in natural systems. As such, an in-depth understanding of the factors controlling the reduction potential of such systems is critical to predicting the likely transformation, transport and fate of these species in natural and perturbed environments. In this study the mineralogy and reduction potential of ferrihydrite suspensions at pH 6.50 and pH 7.00 were determined over the course of their Fe(II)-catalyzed transformation to lepidocrocite and goethite using X-ray absorption spectroscopy and mediated electrochemical approaches. The measured reduction potentials were compared to those of analogous Fe(II)-Fe(III) (oxyhydr)oxide suspensions reacted for 5 min containing pure ferrihydrite (Fh), lepidocrocite (L) and goethite (Gt). The reduction potentials of the pure Fe(II)-Fe(III) (oxyhydr)oxide suspensions were, respectively, +47.5, −13.5 and −122.3 mV vs. SHE at pH 6.5, and −22.9, −84.1 and −189.7 mV vs. SHE at pH 7. These values are in good agreement with reduction potentials calculated using the Nernst equation and reported thermodynamic solubility products indicating that these suspensions had reached equilibrium within 5 min. The reduction potential of the pH 6.50 Fe(II)-ferrihydrite suspension decreased from +47.4 mV to –126.4 mV over a week, and from −20.1 mV to −188.4 mV (all vs. SHE) after 24 h at pH 7. The changes in reduction potential over time matched well to those calculated from the relative proportion of each pure Fe(III) (oxyhydr)oxide present suggesting that Fe 3+ activity was influenced by the mix of iron oxides present rather than the most insoluble solid species. Finally, evidence is provided that adsorbed Fe(II) has the capacity to reduce a significantly larger fraction of a reducible species than the aqueous Fe(II) species with which it is in equilibrium. As an Fe(III) (oxyhydr)oxide suspension in equilibrium with aqueous and adsorbed Fe(II) species possesses a single, unique reduction potential, this suggests that adsorbed Fe(II) is a more facile reductant than aqueous Fe(II). [ABSTRACT FROM AUTHOR]

The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer. Here we postulate that increased sphingomyelin content, developing early in some cancers, recruits and functionalizes plasma membrane ABCB1 conferring a state of partial MDR, which is completed by glycosphingolipid disturbance and the appearance of intracellular vesicular ABCB1. In this review, the independent and interdependent roles of sphingolipid alterations and ABCB1 upregulation during the transformation process and resultant conferment of partial and complete MDR phenotypes are discussed. [ABSTRACT FROM AUTHOR]

Background: Constrained acetabular components have a mechanism to lock in the femoral head. They have been developed to control postoperative dislocation, particularly in revision total hip arthroplasty (THA). Although these components may reduce dislocation, there are durability concerns: with reports of locking mechanism failures and loosening. We wanted to determine the outcome of constrained components in controlling dislocation, and if these components had a higher rate of second revision when compared with standard nonconstrained components.Methods: Revision THA procedures from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) with a recorded primary procedure and initial diagnosis of osteoarthritis were used to compare constrained and standard nonconstrained components. Kaplan-Meier estimates of survivorship were calculated, and hazard ratios using Cox proportional hazard models were used to compare groups.Results: There were 9509 THA first-revision procedures and 700 constrained components. Constrained components had a significantly higher revision rate after 3 months when large-head metal-on-metal components were included (hazard ratio = 1.37; P = .005). When large-head metal-on-metal components were excluded, there was no difference in the rate of second revision between the 2 groups. When the analysis was limited to first revision for dislocation, constrained components had a higher second revision rate for further dislocation after 9 months.Conclusion: Constrained acetabular components had similar second-revision rates when compared with standard nonconstrained components, both for all first-revision reasons and when used to treat dislocation. Although possibly used for the more difficult unstable hips, constrained components had a higher rate of second revision for further dislocation. [ABSTRACT FROM AUTHOR]

Groundwater discharge to the Great Lakes is not well quantified although it may be an important non-point contributor of pollutants to nearshore waters. Poor quantification is in part due to the lack of established field methods for large inland waters, particularly at the regional-scale. This paper evaluates the suitability of radon-222 ( 222 Rn) and local-scale hydraulic gradient methods for quantifying lacustrine groundwater discharge (LGD) into eastern Nottawasaga Bay, Lake Huron, as well as the hydrogeological controls on the observed spatial variability in discharge. A regional-scale 222 Rn survey was first conducted over 17 km of shoreline revealing a potential LGD hotspot area that may be linked to a sand-gravel tunnel valley aquifer system. A 222 Rn mass balance model was applied to estimate groundwater discharge rates (m 3 d − 1 m − 1 of shoreline) over the study area with estimates compared to those calculated based on horizontal and vertical hydraulic gradient measurements. Regional-scale electrical resistivity tomography survey results were consistent with the LGD patterns, illustrating the importance of the lake bed lithology. Overall the cumulative groundwater discharge to eastern Nottawasaga Bay is estimated to be 5–13% of the annual mean discharge from the Notttawasaga River. As pollutant concentrations can be elevated in surficial aquifers compared to tributaries, the contribution of LGD to pollutant loading may be higher than represented by this percentage. Robust approaches to estimate LGD to the Great Lakes including identification of discharge hotspots are needed to predict and effectively manage pollutant inputs to the lakes from groundwater. [ABSTRACT FROM AUTHOR]

Background: Dislocation is a leading cause of revision after primary total hip arthroplasty (THA). Although more common in the first few years after the procedure, dislocation can occur at any time. This study investigated the difference in late dislocation in ceramic-on-ceramic (CoC) bearings compared with metal-on-polyethylene and ceramic-on-polyethylene bearings in THA.Methods: Data were used from the Australian Orthopaedic Association National Joint Replacement Registry, and the cumulative percent revision for dislocation was estimated using the Kaplan-Meier method for the different bearing surfaces. There were 192,275 THAs included in the study with 101,915 metal-on-cross-linked polyethylene (MoXLPE), 30,256 ceramic-on-cross-linked polyethylene (CoXLPE), and 60,104 CoC.Results: The cumulative percent revision for dislocation at 13 years for MoXLPE, CoXLPE, and CoC groups was 1.2 (95% confidence interval [CI], 1.1-1.3), 1.0 (95% CI, 0.7-1.4), and 0.9 (95% CI, 0.8-1.1), respectively. There was an increased risk of revision for dislocation for MoXLPE compared with CoXLPE and CoC. When stratified for head size, there was no difference in the risk of revision for dislocation between MoXLPE, CoXLPE, and CoC in the 28- and 32-mm head sizes. With a head size of 36 mm, MoXLPE had a higher rate of dislocation compared with other materials.Conclusion: Bearing surface has little impact on revision for dislocation. [ABSTRACT FROM AUTHOR]

Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart's contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality. [ABSTRACT FROM AUTHOR]

The hippocampus is believed to be important for rapid learning of arbitrary stimulus-response contingencies, or S-R bindings. In support of this, Schnyer et al. (2006) (Experiment 2) measured priming of reaction times (RTs) to categorise visual objects, and found that patients with medial temporal lobe damage, unlike healthy controls, failed to show evidence of reduced priming when response contingencies were reversed between initial and repeated categorisation of objects (a signature of S-R bindings). We ran a similar though extended object classification task on 6 patients who appear to have selective hippocampal lesions, together with 24 age-matched controls. Unlike Schnyer et al. (2006), we found that reversing response contingencies abolished priming in both controls and patients. Bayes Factors provided no reason to believe that response reversal had less effect on patients than controls. We therefore conclude that it is unlikely that the hippocampus is needed for S-R bindings. [ABSTRACT FROM AUTHOR]

Background Retransplantation has emerged as a therapeutic option for patients experiencing respiratory failure after single lung transplantation. However, outcomes associated with the surgical option (ipsilateral, contralateral, or bilateral lung retransplantation) has not been well evaluated. Methods The Organ Procurement and Transplantation Network database (1994 to 2012) was queried for all lung transplant procedures performed after an initial single lung transplantation. Donor and recipient demographics, before and after transplant characteristics, and outcomes were stratified by retransplant procedural choice and by interval between transplants. Risk factors for mortality were evaluated by Cox proportional hazards regression analysis. Results Of 325 prior single lung transplant recipients, 50 underwent ipsilateral, 175 contralateral, and 100 bilateral lung retransplantation. The number of retransplant procedures performed per year increased from 3 in 1994 to 31 in 2012, with an increasing proportion of contralateral retransplantation and declining proportions of ipsilateral and bilateral retransplantation. Survival was significantly better in the contralateral and bilateral retransplant groups than in the ipsilateral retransplant group at 30 days (94% and 89% versus 80%), 1 year (72% and 67% versus 50%), and 5 years (41% and 42% versus 20%). Ipsilateral retransplantation (hazard ratio 1.48; p = 0.042), mechanical ventilation before retransplant (hazard ratio 2.39; p < 0.001), and retransplantation performed in the first half of the study period (hazard ratio 1.45; p = 0.027) were associated with increased mortality. Conclusions After an initial single lung transplant, both the incidence of retransplantation and postoperative survival have increased with time. Although ipsilateral lung retransplantation may be the best available alternative in particular circumstances, this analysis suggests that contralateral or bilateral lung retransplantation may be preferable in patients for whom those options are medically sensible. [ABSTRACT FROM AUTHOR]

The use of leaderboards is a common approach to the gamification of employee performance, but little is known about the specific mechanisms and mediating processes by which leaderboards actually affect employee behavior. Given the lack of research in this domain, this study proposes goal-setting theory, one of the most well-established motivational theories in psychology, as a framework by which to understand these effects. In this study, a classic brainstorming task is gamified with a leaderboard in order to explore this. Participants were randomly assigned to four classic levels of goal-setting (do-your-best, easy, difficult and impossible goals) plus a leaderboard populated with initials and scores representing identical goal-setting conditions. The presence of a leaderboard was successful in motivating participants to performance levels similar to that of difficult and impossible goal-setting, suggesting participants implicitly set goals at or near the top of the leaderboard without any prompting to do so. Goal commitment, a common individual difference moderator in goal-setting theory, was also assessed and behaved similarly in the presence of the leaderboard as when traditional goals were provided. From these results, we conclude that goal-setting theory is valuable to understand the success of leaderboards, and we recommend further exploration of existing psychological theories, including goal-setting, to better explain the effects of gamification. [ABSTRACT FROM AUTHOR]

Background Gamification, the use of game elements in non-game contexts, has become a popular technique to improve instructional outcomes in both organizational and educational contexts. In the organizational context, the Technology-Enhanced Training Effectiveness Model [TETEM] provides a framework to understand how technologies, like gamification, can effect change in various instructional outcomes. Specifically, application of TETEM suggests that gamification may not effect change in instructional outcomes when learner attitudes towards game-based learning and experience with video games are low. Method In this study, we test this model in the gamification context by assigning potential learners to read scenarios describing gamified instruction or traditional, PowerPoint instruction in a random order and assessing their training valence. Results On average, participants anticipated greater value from gamified instruction, but as predicted by TETEM, this effect was moderated by both video game experience and attitudes towards game-based learning. Among potential learners with high experience and attitudes, gamification produces better outcomes than PowerPoint, but among potential learners with low experience and attitudes, gamification produces worse outcomes than PowerPoint. Implications We provide empirical support for TETEM and conclude that for gamification to be successful, the attitudes and experience of participants must be assessed and ensured before gamification is implemented. [ABSTRACT FROM AUTHOR]

Context Premenopausal women have blunted counter-regulatory hormone responses (CRR) to hypoglycemia compared to men. Postmenopausal women have CRR similar to men; the premenopausal pattern can be restored by estrogen. However, glucagon and pancreatic polypeptide (PP) responses remain lower in postmenopausal women than in men. Since hyperandrogenemia contributes to the metabolic phenotype of polycystic ovary syndrome (PCOS), we hypothesize that CRR to hypoglycemia especially of glucagon and PP is exaggerated in premenopausal women with PCOS compared to premenopausal control women. Study Subjects and Methods Ten obese women with PCOS and 9 control women of similar ethnicity, age and BMI underwent determination of CRR in response to hypoglycemia during 180-min 60 mU/m 2 /min insulin dose hypoglycemic clamp with isotopic assessment of endogenous glucose production (EGP). To assess CRR to hypoglycemia, glucagon, cortisol, growth hormone (GH), epinephrine, norepinephrine, PP, lactate, free fatty acid (FFA), β-hydroxybutyrate, and glycerol levels were sampled at 15-min intervals throughout the clamp. Main Findings Incremental glucagon levels were ~ 3-fold higher during hypoglycemia ( P = 0.03) in PCOS. Postabsorptive, steady-state and incremental GH, cortisol, epinephrine, norepinephrine, PP, FFA, glycerol and β-hydroxybutyrate did not differ. At target glucose levels of ~ 52 mg/dL, insulin mediated glucose disposal (IMGD) was decreased by ~ 40% ( P = 0.02) in PCOS, compared to control women, despite ~ 20% higher steady-state insulin levels ( P = 0.03). Neither postabsorptive nor steady-state EGP differed. However, postabsorptive lactate levels were ~ 50% higher ( P = 0.02). PCOS status ( P = 0.04) and IMGD ( P = 0.02) predicted the differential glucagon response to hypoglycemia in separate regression models, however, neither parameter remained an independent predictor in a combined model. Principal Conclusions Glucagon responses were increased in PCOS, whereas other CRR did not differ. Women with PCOS were insulin resistant under hypoglycemic conditions and higher postabsorptive lactate levels in PCOS were consistent with this finding. Insulin resistance may have contributed to exaggerated glucagon response to hypoglycemia in PCOS. [ABSTRACT FROM AUTHOR]

Background Hospital and surgeon volume each have an association with postoperative outcomes. The volume of lung cancer surgery at our Veterans Administration Medical Center (VAMC) is lower than at our academic medical center (AMC). We compared the outcomes after lobectomy at VAMC versus AMC to identify specific areas of clinical care requiring quality improvement. Methods To keep surgeon experience constant, data were derived from a prospective database from a single surgeon. Included were all male patients undergoing lobectomy for non-small cell lung cancer. Postoperative morbidity, mortality, and overall survival were compared after propensity score matching. Results From 2004 to 2013, 419 patients were evaluated (338 AMC, 81 VAMC). Outcomes comparison after propensity score matching of 81 AMC patients with 81 VAMC patients found a higher rate of major complications (12% versus 27%, p = 0.02) and longer hospital stay (median 6.0 versus 7.5 days, p < 0.001) for VAMC, but no difference in 90-day mortality (AMC 5% versus VAMC 6%, p > 0.99). Pneumonia was the specific complication found to be higher at VAMC (11% versus AMC 1.2%, p = 0.01). There was no difference in 5-year overall survival for stage I disease (AMC 68% versus VAMC 69%, p = 0.95). Conclusions Keeping surgeon experience constant, and after adjusting for patient factors, the rate of major complication after lobectomy is higher at VAMC. The difference is largely attributable to a higher rate of postoperative pneumonia at VAMC. Complications after pulmonary resection at VAMC could be reduced by implementing quality improvement initiatives aimed at reducing the rate of postoperative pneumonia. [ABSTRACT FROM AUTHOR]

Far northern California forests are highly biodiverse in wildlife reservoirs and arthropod vectors that may propagate rickettsial pathogens in nature. The proximity of small rural communities to these forests puts people and domestic animals at risk of vector-borne infection due to spillover from wildlife. The current study was conducted to document exposure to rickettsial pathogens in people and domestic animals in a rural community, and identify which rickettsiae are present in sylvatic and peri-domestic environments near this community. Blood samples from people, domestic animals (dogs, cats, and horses) and wild carnivores were tested for Rickettsia spp. antibodies and DNA (people and domestic animals only) by serology and real time (RT)-PCR, respectively. Ectoparasites were collected from dogs, wild carnivores and from vegetation by flagging, and tested for Rickettsia spp. DNA by RT-PCR. DNA sequencing of the rickettsial 17 kDa protein gene or the ompA gene was used for species identification. Despite a seroprevalence of 3% in people, 42% in dogs, 79% in cats, 33% in gray foxes, and 83% in bobcats, RT-PCR on blood was consistently negative, likely because the sensitivity of this test is low, as Rickettsia spp. do not often circulate in high numbers in the blood. Rickettsia spp. DNA was found in four flea species collected from bobcats and Ctenocephalides felis collected from domestic dogs. All amplicons sequenced from fleas were R. felis . Ixodes pacificus collected by flagging were commonly infected with a Rickettsia sp. endosymbiont. Rickettsia rhipicephali DNA was found in Dermacentor variabilis from dogs, black bears, a gray fox, and a D. occidentalis collected by flagging. Dermacentor variabilis from dogs and black bears also contained R. montanensis DNA. Multiple Rickettsia spp. (including species with zoonotic and pathogenic potential) were found among human biting arthropod vectors of both wild and domestic carnivores and on flags. Knowledge of the diversity of Rickettsia spp. that are present within arthropod vectors to which people and domestic animals are exposed is an essential first step is making an accurate diagnosis and in better understanding the epidemiology of these potential pathogens. Within-host and vector interaction among these species may play a role in spillover into human and domestic animals. [ABSTRACT FROM AUTHOR]

How does the developing brain respond to recent experience? Repetition suppression (RS) is a robust and well-characterized response of to recent experience found, predominantly, in the perceptual cortices of the adult brain. We use functional near-infrared spectroscopy (fNIRS) to investigate how perceptual (temporal and occipital) and frontal cortices in the infant brain respond to auditory and visual stimulus repetitions (spoken words and faces). In Experiment 1, we find strong evidence of repetition suppression in the frontal cortex but only for auditory stimuli. In perceptual cortices, we find only suggestive evidence of auditory RS in the temporal cortex and no evidence of visual RS in any ROI. In Experiments 2 and 3, we replicate and extend these findings. Overall, we provide the first evidence that infant and adult brains respond differently to stimulus repetition. We suggest that the frontal lobe may support the development of RS in perceptual cortices. [ABSTRACT FROM AUTHOR]

The kidney allocation system that took effect on December 4, 2014 represents a significant improvement over the prior approach. It seeks to improve outcomes by longevity matching — pairing kidneys expected to function the longest with recipients expected to live the longest. It addresses the biological barriers faced by highly sensitized patients in an evidence based fashion and it begins to introduce the concept of medical need into kidney allocation by crediting time from the starting dialysis to a patient's waiting time. Additionally, it adds a more granular and continuous approach to classifying deceased donor kidneys through the kidney donor profile index and moves away from the dichotomous and flawed, standard criteria/extended criteria approach to allocating kidneys. Despite these changes, access to kidney transplantation across the age spectrum has remained intact and equitable. However even with these numerous positive improvements the system is not without its flaws. The increased sharing and by extension shipping of kidneys have created logistical challenges for organ procurement organizations and transplant centers. Early results seem to indicate that there have been an increase in cold ischemic time, an increase in delayed graft function and an increase in organ discard rate. There is also a reduced offer rate for children and while not a statistically significant decline in the number of transplants, it is a trend that requires close monitoring. Finally, the new kidney allocation system has done nothing to address the glaring deficiencies in the multi-organ allocation practices, all of which include a kidney, in the United States. Therefore despite the improvements made in kidney allocation, there is work yet to be done to ensure that the allocation of life saving and life prolonging organs for transplantation is done in a fashion consistent with ethical principles, based on science and free from local self interest so that this national resource is used for the betterment of the population it is meant to serve. [ABSTRACT FROM AUTHOR]

The energy released by failure of rechargeable 18-mm diameter by 65-mm long cylindrical (18650) lithium ion cells/batteries was measured in a bomb calorimeter for 4 different commercial cathode chemistries over the full range of charge using a method developed for this purpose. Thermal runaway was induced by electrical resistance (Joule) heating of the cell in the nitrogen-filled pressure vessel (bomb) to preclude combustion. The total energy released by cell failure, Δ H f , was assumed to be comprised of the stored electrical energy E (cell potential × charge) and the chemical energy of mixing, reaction and thermal decomposition of the cell components, Δ U rxn . The contribution of E and Δ U rxn to Δ H f was determined and the mass of volatile, combustible thermal decomposition products was measured in an effort to characterize the fire safety hazard of rechargeable lithium ion cells. [ABSTRACT FROM AUTHOR]

The use and development of the investigative tool colloquially known as criminal profiling has steadily increased over the past five decades throughout the world. Coupled with this growth has been a diversification in the suggested range of applications for this technique. Possibly the most notable of these has been the attempted transition of the technique from a tool intended to assist police investigations into a form of expert witness evidence admissible in legal proceedings. Whilst case law in various jurisdictions has considered with mutual disinclination the evidentiary admissibility of criminal profiling, a disjunction has evolved between these judicial examinations and the scientifically vetted research testing the accuracy (i.e., validity) of the technique. This article offers an analysis of the research directly testing the validity of the criminal profiling technique and the extant legal principles considering its evidentiary admissibility. This analysis reveals that research findings concerning the validity of criminal profiling are surprisingly compatible with the extant legal principles. The overall conclusion is that a discrete form of crime behavioural analysis is supported by the profiler validity research and could be regarded as potentially admissible expert witness evidence. Finally, a number of theoretical connections are also identified concerning the skills and qualifications of individuals who may feasibly provide such expert testimony. [ABSTRACT FROM AUTHOR]

Heart failure, whether acute or chronic, remains a major health care crisis affecting almost 6 million Americans and over 23 million people worldwide. Roughly half of those affected will die within 5 years, and the annual cost exceeds $30 billion in the US alone. Although medical therapy has made some modest inroads in partially stemming the heart failure tsunami, there remains a significant population for whom medication is unsuccessful or has ceased being effective; such patients can benefit from heart transplantation or mechanical circulatory support. Indeed, in the past quarter century (and as covered in Cardiovascular Pathology over those years), significant improvements in pathologic understanding and in engineering design have materially enhanced the toolkit of options for such refractory patients. Mechanical devices, whether total artificial hearts or ventricular assist devices, have been reengineered to reduce complications and basic wear and tear. Transplant survival has also been extended through a better comprehension of and improved therapies for transplant vasculopathy and antibody-mediated rejection. Here we review the ideas and treatments from the last 25 years and highlight some of the new directions in nonpharmacologic heart failure therapy. [ABSTRACT FROM AUTHOR]

A 2011 randomized controlled trial compared the effectiveness of two brief motivation-enhancing therapy (MET) models among alcohol-positive adolescents in an urban emergency department: adolescent MET-only versus MET + Family Check-Up (FCU), a parent MET model. Results indicated that among the 97 adolescents completing the 3-month assessment, both conditions were associated with reduced drinking and MET+FCU was associated with lower rates of high volume drinking than adolescent MET-only. The goal of this study was to identify predictors and moderators of high volume drinking in the original trial. Seven candidate variables were evaluated as moderators across three domains: demographic characteristics, psychological factors, and socio-contextual factors. Analyses of covariance models identified one significant predictor and one significant moderator of outcome. Older adolescents had significantly worse drinking outcomes than younger adolescents regardless of MET condition. Adolescents whose parents screened positive for problematic alcohol use at baseline had significantly worse drinking outcomes in the MET+FCU condition than the MET-only condition. Results indicate that alcohol-positive adolescents presenting to the emergency department may respond better to MET models if they are under the age of 16. Involving parents who have problematic alcohol use in a parent-focused MET may have negative effects on adolescent high volume drinking. [ABSTRACT FROM AUTHOR]

Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the mechanical properties of normal and osteoarthritic human articular cartilage and enhances our ability to model this tissue using simple isotropic hyperelastic materials. [ABSTRACT FROM AUTHOR]