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Background: Grape phylloxera (Daktulosphaira vitifoliae Fitch) is a major insect pest that negatively impacts commercial grapevine performance worldwide. Consequently, the use of phylloxera resistant rootstocks is an essential component of vineyard management. However, the majority of commercially available rootstocks used in viticulture production provide limited levels of grape phylloxera resistance, in part due to the adaptation of phylloxera biotypes to different Vitis species. Therefore, there is pressing need to develop new rootstocks better adapted to specific grape growing regions with complete resistance to grape phylloxera biotypes., Results: Grapevine rootstock breeding material, including an accession of Vitis cinerea and V. aestivalis, DRX55 ([M. rotundifolia x V. vinifera] x open pollinated) and MS27-31 (M. rotundifolia specific hybrid), provided complete resistance to grape phylloxera in potted plant assays. To map the genetic factor(s) of grape phylloxera resistance, a F 1 V. cinerea x V. vinifera Riesling population was screened for resistance. Heritability analysis indicates that the V. cinerea accession contained a single allele referred as RESISTANCE TO DAKTULOSPHAIRA VITIFOLIAE 2 (RDV2) that confers grape phylloxera resistance. Using genetic maps constructed with pseudo-testcross markers for V. cinerea and Riesling, a single phylloxera resistance locus was identified in V. cinerea. After validating SNPs at the RDV2 locus, interval and linkage mapping showed that grape phylloxera resistance mapped to linkage group 14 at position 16.7 cM., Conclusion: The mapping of RDV2 and the validation of markers linked to grape phylloxera resistance provides the basis to breed new rootstocks via marker-assisted selection that improve vineyard performance.

Background: The incidence of surgical site infection (SSI) has become a key quality indicator following clean and clean/contaminated surgical procedures. In contrast, contaminated and dirty wounds have garnered little attention with this quality metric because of the expected higher complication incidence. We hypothesized that wound management strategies in this high-risk population vary significantly and might not add value to the overall care., Materials and Methods: This is a retrospective, observational study of trauma patients who underwent an exploratory laparotomy at an urban, academic, level 1 trauma center from 2014 to 2016. Deaths before hospital discharge were excluded. Wounds were classified using the Centers for Disease Control and Prevention definition on review of the operative reports. SSI was determined by review of the medical record, also per Centers for Disease Control and Prevention definition. Wound management strategies were categorized as either primary skin closure or closure by secondary intention. Outcomes were compared using Chi square or Kruskal-Wallis test., Results: There were 128 patients who met study criteria. Fifty-five (42.9%) wounds were left open to close by secondary intention. In the wounds that were closed primarily (n = 73), eight (10.9%) developed an SSI. There were significant differences in the average length of stay (25.0 versus 11.6 d, P = 0.032), number of office visits (3.0 versus 1.8, P = 0.008), and time from last laparotomy to the last wound care office visit (112.8 versus 57.4, P = 0.012) between patients who were treated with secondary intention closure compared to those closed primarily who did not suffer from SSI., Conclusions: There is significant incidence of SSI in contaminated and dirty traumatic abdominal wounds; however, wound management strategies vary widely within this cohort. Closure by secondary intention requires significantly more resource utilization. Isolating risk factors for SSI may allow additional patients to undergo primary skin closure and avoid the morbidity of closure by secondary intention., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of the present study was to examine regional differences in average self-reported BMI, obesity prevalence, and frequent exercise (FE) among members of Team Red, White, and Blue (Team RWB) - a military veteran service organization founded to increase physical activity in veterans. A total of 10,015 military veterans participated in a needs assessment conducted by Team RWB between December 2014 and August 2016. Multivariate regression analysis with bootstrapped coefficients revealed that: BMI was highest in the Midwest region ( M  = 28.282) of the United States, F (20, 9882)  = 105.560, p  < 0.001; obesity prevalence was highest in the Southcentral (32.300%) and Southeast (32.200%) regions, x 2 (9731)  = 10,850, p  < 0.001; and FE was most prevalent in the Mid-Atlantic region (67.3%), x 2 (9882)  = 11,291, p  < 0.001.The results of this study closely mirror results found in studies of the general population. A better understanding of the geographic distribution of these outcomes could guide the targeting of sub-populations for public health programs. In particular, Team Red, White & Blue community growth and other fitness based public health programs could be expanded to reach more veterans.

Background: The relationship between high volume and improved outcomes has been described for a host of elective high-impact, low-frequency procedures, but there are little data to support such a relationship in high-impact low-frequency procedures in trauma. Using emergency department thoracotomy (EDT) as a model, we hypothesized that patients presenting to centers with higher institutional volumes of EDT would have improved survival referent to those presenting to lower volume institutions., Methods: We queried the Pennsylvania Trauma Outcomes Study registry from 2007 to 2015 for all EDTs performed at Level I and II centers identified by ICD-9 procedure codes and a location stamp indicating the emergency department. We examined patient-level risk factors for survival in univariate regression and multivariable regression models. Centers were divided into tertiles of mean annual EDT volume, and the association between mean annual EDT volume and patient survival was examined using logistic regression after controlling for patient factors., Results: 1,399 EDTs were performed at 28 centers. Overall survival was 6.8%. After controlling for patient age, mechanism of injury, signs of life, and injury severity, patients presenting to centers in the highest tertile of volume had significantly higher odds of survival compared with patients presenting to centers in the lowest tertile of volume (OR 4.56, 95% CI 1.43-14.50)., Conclusions: Patients presenting to centers with higher mean annual volume of EDTs have improved survival compared with those presenting to institutions with lower mean annual EDT volume. Efforts to understand the etiology of this finding may lead to interventions to improve outcomes at lower-volume centers., Level of Evidence: Prognostic/Epidemiological, level III; Therapeutic, level IV.

Military service assimilates individuals into a socially cohesive force to address dangerous and traumatic situations that have no counterpart in civilian life. Upon leaving active duty, many veterans experience a "reverse culture shock" when trying to reintegrate into civilian institutions and cultivate supportive social networks. Poor social reintegration is associated with greater morbidity and premature mortality in part due to adoption of risky health behaviors, social isolation, and inadequate engagement in health care services. Although institutions like the Veterans Health Administration (VA) do much to address the complex psychosocial and health care needs of veterans and their families with evidence-based care, only 61% of Operations Enduring and Iraqi Freedom (OEF/OIF) Veterans are enrolled in VA care and there are numerous perceived barriers to care for enrollees. To address this gap, a community-based nonprofit organization, Team Red, White & Blue (RWB), was created to help veterans establish health-enriching social connections with communities through the consistent provision of inclusive and locally tailored physical, social, and service activities. This article provides an overview of the development and refinement of a theory-based framework for veteran health called the Enrichment Equation, comprised of three core constructs: health, people, and purpose. By operationalizing programming activities and roles, we describe how theoretical components were translated into a social networking implementation package that enabled rapid national spread of Team RWB. We conclude with future opportunities to partner with researchers and other organizations to understand program impact, and to identify effective intervention components that could be adapted for similar vulnerable groups.

Introduction: Little is known regarding the confidence of military surgeons prior to combat zone deployment. Military surgeons are frequently deployed without peers experienced in combat surgery. We hypothesized that forward surgical team experience (FSTE) increases surgeon confidence with critical skill sets., Methods: We conducted a national survey of military affiliated personnel. We used a novel survey instrument that was piloted and validated by experienced military surgeons to collect demographics, education, practice patterns, and confidence parameters for trauma and surgical critical care skills. Skills were defined as crucial operative techniques for hemorrhage control and resuscitation. Surveyors were blinded to participants, and surveys were returned electronically via REDCap database. Data were analyzed with SPSS using appropriate models. Significance was considered p < 0.05., Results: Of 174 distributed surveys, 86 were completed. Nine individuals failed to characterize their FSTE, thus leaving a sample size of 77. At the time of first deployment, 78.4% were alone or with less experienced surgeons and 53.2% had less than 2 yr of post-residency practice. The respondents' confidence in damage control techniques and seven other trauma skills increased relative to FSTE. After adjusting for years of practice, number of trauma resuscitations performed per month and pre-deployment training, there remained a significant positive association between FSTE and confidence in damage control, thoracic surgery, extremity/junctional hemorrhage control, trauma systems administration, adult critical care and airway management., Conclusions: Training programs and years of general surgery practice do not replace FSTE among military surgeons. Pre-deployment training that mimics FST skill sets should be developed to improve military surgeon confidence and outcomes., Level of Evidence: Prognostic and Epidemiologic, Level IV.

Introduction: Surgical Intensive Care Unit (SICU) patients "boarding" in ICUs other than the designated home unit have been shown to suffer increased rates of complications. We hypothesized that ICU rounding practices are different when SICU patients are housed in home vs. boarding ICUs., Material and Methods: SICU rounds were observed at an academic quaternary medical center. Individual patient rounding time and order seen on rounds along with patient data and demographics were recorded. Multivariable regression analysis was used for comparison between patients., Results: Non-boarders were older, observed on a later post ICU admission day and were more likely to be mechanically ventilated. Boarded patients were often seen at the end of rounds and for less time. Not being a boarder, age, APACHE II score on admission, vasopressor use, and positive pressure ventilation all predicted increased rounding time., Conclusions: Surgical ICU patients boarding in non-preferred units are often seen at the end of rounds, result in a greater reliance upon telephone communication, and receive less bedside attention from ICU provider teams., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Residential characteristics in urban neighborhoods impact health and might be important factors contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in African American women. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies including populations of African American women, setting in "urban" areas, and a measure of a neighborhood or residential factor were reviewed. Four parameters related to neighborhood or residential factors were extracted including: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. Our analysis showed that African American women living in low nSES have greater odds of late stage diagnosis and mortality. Furthermore, African American women living in segregated areas (higher percentage of Blacks) have higher odds of late stage diagnosis and mortality compared to White and Hispanic women living in less segregated areas (lower percentage of Blacks). Late stage diagnosis was also shown to be significantly higher in areas with poor mammography access and areas with higher Black residential segregation. Lastly, residential pollution did not affect breast cancer risk in African American women. Overall, this systematic review provides a qualitative synthesis of major neighborhood and residential factors on breast cancer outcomes in African American women.

Background and Objectives: Correlational research shows that belief in a continuum of psychiatric problems predicts decreased public stigma. However, the correlational findings fail to inform the stigma reduction prospects of manipulating continuum beliefs. All extant experimental work has been executed online. This study examined effects of a laboratory-based continuum intervention on behavioral and self-report measures of psychiatric stigma., Methods: Sixty-nine undergraduates believed that they would meet a man with schizophrenia. They then read a bogus scientific article that attested to a categorical view of schizophrenia, a continuum view, or that merely described schizophrenia. Some participants then completed a task that required reflection on their differences from (categorical group) or similarities to (continuum group) the man with schizophrenia. Participants eventually moved to an adjacent room and sat in one of several seats that varied in their proximity to a seat ostensibly occupied by the man with schizophrenia., Results: The continuum intervention decreased self-reported social distance and the categorical intervention increased endorsement of damaging stereotypes. Seat selection was unaffected by our manipulation, but we obtained evidence of significant links to validated stigma measures., Limitations: Our sample was small, and our behavioral stigma measure could be modified to maximize variability in participants' seat selection., Conclusions: The study offers modest support of the stigma reduction effect of continuum belief intervention. It offers new evidence of the pernicious consequences of interventions that inflate perceptions of the "otherness" of individuals with psychiatric problems. Finally, it shines new light on stigma-related behavior measurable in the laboratory., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT., Methods: From 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy., Results: A total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy., Conclusion: Expectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations., Level of Evidence: Prognostic/epidemiologic study, level III; Therapeutic study, level IV.

Plant parasitic nematodes, including root knot nematode Meloidogyne species, cause extensive damage to agriculture and horticultural crops. As Vitis vinifera cultivars are susceptible to root knot nematode parasitism, rootstocks resistant to these soil pests provide a sustainable approach to maintain grapevine production. Currently, most of the commercially available root knot nematode resistant rootstocks are highly vigorous and take up excess potassium, which reduces wine quality. As a result, there is a pressing need to breed new root knot nematode resistant rootstocks, which have no impact on wine quality. To develop molecular markers that predict root knot nematode resistance for marker assisted breeding, a genetic approach was employed to identify a root knot nematode resistance locus in grapevine. To this end, a Meloidogyne javanica resistant Vitis cinerea accession was crossed to a susceptible Vitis vinifera cultivar Riesling and results from screening the F1 individuals support a model that root knot nematode resistance, is conferred by a single dominant allele, referred as MELOIDOGYNE JAVANICA RESISTANCE1 (MJR1). Further, MJR1 resistance appears to be mediated by a hypersensitive response that occurs in the root apical meristem. Single nucleotide polymorphisms (SNPs) were identified using genotyping-by-sequencing and results from association and genetic mapping identified the MJR1 locus, which is located on chromosome 18 in the Vitis cinerea accession. Validation of the SNPs linked to the MJR1 locus using a Sequenom MassARRAY platform found that only 50% could be validated. The validated SNPs that flank and co-segregate with the MJR1 locus can be used for marker-assisted selection for Meloidogyne javanica resistance in grapevine.

The bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after ovariectomy. However, its impact on the liver transcriptomes associated with prevention of hepatosteatosis is yet to be determined. In the present study, we use liver transcriptomics and plasma metabolomics analysis to characterize the effects of various estrogens on liver. The CE+BZA combination was very effective at preventing ovariectomy-induced weight gain in mice fed a high-fat diet (HFD). In CE+BZA treated animals, liver weight and hepatic lipid deposition were significantly lower than in Vehicle (Veh) treated animals. Additionally, CE+BZA induced unique liver transcriptome and plasma metabolome profiles compared to estradiol, conjugated estrogens alone, and bazedoxifene alone. Blood plasma metabolite analysis identified several metabolites similar to and distinct from other estrogen treatments. Integrated pathway analysis showed that gene networks that were associated with inflammation, reactive oxygen species pathway and lipid metabolism and their relevant metabolites were regulated significantly by CE+BZA treatment. Thus, long-term CE+BZA treatment modulated hepatic metabolic gene networks and their associated metabolites and improves hepatic health without stimulating the uterus.

Background: Venous thromboembolism (VTE) after major vascular injury (MVI) is particularly challenging because the competing risk of thrombosis and embolization after direct vessel injury must be balanced with risk of bleeding after surgical repair. We hypothesized that venous injuries, repair type, and intraoperative anticoagulation would influence VTE formation after MVI., Methods: A multi-institution, retrospective cohort study of consecutive MVI patients was conducted at three urban, Level I centers (2005-2013). Patients with MVI of the neck, torso, or proximal extremities (to elbows/knees) were included. Our primary study endpoint was the development of VTE (DVT or pulmonary embolism [PE])., Results: The 435 major vascular injury patients were primarily young (27 years) men (89%) with penetrating (84%) injuries. When patients with (n = 108) and without (n = 327) VTE were compared, we observed no difference in age, mechanism, extremity injury, tourniquet use, orthopedic and spine injuries, damage control, local heparinized saline, or vascular surgery consultation (all p > 0.05). VTE patients had greater Injury Severity Score (ISS) (17 vs. 12), shock indices (1 vs. 0.9), and more torso (58% vs. 35%) and venous (73% vs. 48%) injuries, but less often received systemic intraoperative anticoagulation (39% vs. 53%) or postoperative enoxaparin (47% vs. 61%) prophylaxis (all p < 0.05). After controlling for ISS, hemodynamics, injured vessel, intraoperative anticoagulation, and postoperative prophylaxis, multivariable analysis revealed venous injury was independently predictive of VTE (odds ratio, 2.7; p = 0.002). Multivariable analysis of the venous injuries subset (n = 237) then determined that only delay in starting VTE chemoprophylaxis (odds ratio, 1.3/day; p = 0.013) independently predicted VTE after controlling for ISS, hemodynamics, injured vessel, surgical subspecialty, intraoperative anticoagulation, and postoperative prophylaxis. Overall, 3.4% of venous injury patients developed PE, but PE rates were not related to their operative management (p = 0.72)., Conclusion: Patients with major venous injuries are at high risk for VTE, regardless of intraoperative management. Our results support the immediate initiation of postoperative chemoprophylaxis in patients with major venous injuries., Level of Evidence: Therapeutic/care management, level IV.

Human sleeping arrangements have evolved over time and differ across cultures. The majority of adults share their bed at one time or another with a partner or child, and many also sleep with pets. In fact, around half of dog and cat owners report sharing a bed or bedroom with their pet(s). However, interspecies co-sleeping has been trivialized in the literature relative to interpersonal or human-human co-sleeping, receiving little attention from an interdisciplinary psychological perspective. In this paper, we provide a historical outline of the "civilizing process" that has led to current sociocultural conceptions of sleep as an individual, private function crucial for the functioning of society and the health of individuals. We identify similar historical processes at work in the formation of contemporary constructions of socially normative sleeping arrangements for humans and animals. Importantly, since previous examinations of co-sleeping practices have anthropocentrically framed this topic, the result is an incomplete understanding of co-sleeping practices. By using dogs as an exemplar of human-animal co-sleeping, and comparing human-canine sleeping with adult-child co-sleeping, we determine that both forms of co-sleeping share common factors for establishment and maintenance, and often result in similar benefits and drawbacks. We propose that human-animal and adult-child co-sleeping should be approached as legitimate and socially relevant forms of co-sleeping, and we recommend that co-sleeping be approached broadly as a social practice involving relations with humans and other animals. Because our proposition is speculative and derived from canine-centric data, we recommend ongoing theoretical refinement grounded in empirical research addressing co-sleeping between humans and multiple animal species.

Background: Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any hypocalcemia or hypercalcemia (either primary or from overcorrection) in the first 24 hours after severe injury is associated with increased mortality., Methods: All patients at our institution with massive transfusion protocol activation from January 2013 through December 2014 were identified. Patients transferred from another hospital, those not transfused, those with no ionized calcium (Ca) measured, and those who expired in the trauma bay were excluded. Hypocalcemia and hypercalcemia were defined as any level outside the normal range of Ca at our institution (1-1.25 mmol/L). Receiver operator curve analysis was also used to further examine significant thresholds for both hypocalcemia and hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes included advanced cardiovascular life support, damage control surgery, ventilator days, and intensive care unit days., Results: The massive transfusion protocol was activated for 77 patients of whom 36 were excluded leaving 41 for analysis. Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%). Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P = .13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P < .01). Receiver operator curve analysis identified inflection points in mortality outside a Ca range of 0.84 to 1.30 mmol/L. Using these extreme values, 15 (37%) had hypocalcemia with a 60% mortality (vs 4%; P < .01) and 9 (22%) had hypercalcemia with a 78% mortality (vs 9%; P < .01). Patients with extreme hypocalcemia and hypercalcemia also received more red blood cells, plasma, platelets, and calcium repletion., Conclusions: Hypocalcemia and hypercalcemia occur commonly during the initial resuscitation of severely injured patients. Mild hypocalcemia may be tolerable, but more extreme hypocalcemia and any hypercalcemia should be avoided. Further assessment to define best practice for calcium management during resuscitation is warranted.

Purpose: To analyze in-room video recordings of operating room (OR) to intensive care unit (ICU) handoffs to determine tempo and quality of team interactions on nights and weekends compared with weekdays, and to demonstrate how existing telemedicine technology can be used to evaluate handoffs., Method: This prospective observational study of OR-to-ICU bedside handoffs was conducted in the surgical ICU of the Hospital of the University of Pennsylvania in July 2014-January 2015. Handoff video recordings were obtained for quality improvement purposes using existing telemedicine cameras. Evaluators used adapted validated in-person assessment measures to analyze basic characteristics and quality measures (timing, report types, report duration, presence of physical exam, teamwork skills, engagement, report delivery skills, listening skills, interruptions, unprofessional comments or actions)., Results: Sixteen weekday and 16 night and weekend handoffs were compared. There were no significant differences in basic characteristics. Most quality measures were similar on weekdays compared with nights and weekends. Surgeons demonstrated better report delivery skills and engagement on nights and weekends (P = .002 and P = .04, respectively), whereas OR anesthesiologists' scores were similar during both time frames., Conclusions: This study presents a novel approach of assessing handoff quality in OR-to-ICU handoffs using an existing telemedicine infrastructure. Using this approach, quality measures of night and weekend handoffs were found to be no worse-and sometimes better-than those during weekdays. Video analysis may emerge as an ideal unobtrusive quality improvement methodology to monitor handoffs and improve education and compliance with institutional handoff policies.

Our understanding of the frequency and duration of maternal care behaviours in the domestic dog during the first two postnatal weeks is limited, largely due to the inconsistencies in the sampling methodologies that have been employed. In order to develop a more concise picture of maternal care behaviour during this period, and to help establish the sampling method that represents these behaviours best, we compared a variety of time sampling methods Six litters were continuously observed for a total of 96h over postnatal days 3, 6, 9 and 12 (24h per day). Frequent (dam presence, nursing duration, contact duration) and infrequent maternal behaviours (anogenital licking duration and frequency) were coded using five different time sampling methods that included: 12-h night (1800-0600h), 12-h day (0600-1800h), one hour period during the night (1800-0600h), one hour period during the day (0600-1800h) and a one hour period anytime. Each of the one hour time sampling method consisted of four randomly chosen 15-min periods. Two random sets of four 15-min period were also analysed to ensure reliability. We then determined which of the time sampling methods averaged over the three 24-h periods best represented the frequency and duration of behaviours. As might be expected, frequently occurring behaviours were adequately represented by short (oneh) sampling periods, however this was not the case with the infrequent behaviour. Thus, we argue that the time sampling methodology employed must match the behaviour of interest. This caution applies to maternal behaviour in altricial species, such as canids, as well as all systematic behavioural observations utilising time sampling methodology., (Copyright © 2017. Published by Elsevier B.V.)

Background: Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH., Methods: Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations., Results: Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations., Conclusions: Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Operating room (OR) to intensive care unit (ICU) handoffs are complex and known to be associated with adverse events and patient harm. The authors hypothesized that handoff quality diminishes during nights/weekends and that bedside handoff practices are similar between ICUs of the same health system. Bedside OR-to-ICU handoffs were directly observed in 2 surgical ICUs with different patient volumes. Handoff quality measures were compared within the ICUs on weekdays versus nights/weekends as well as between the high- and moderate-volume ICUs. In the high-volume ICU, transmitter delivery scores were significantly better during off hours, while other measures were not different. High-volume ICU scores were consistently better than those in the moderate-volume ICU. Bedside handoff practices are not worse during off hours and may be better in ICUs used to a higher patient volume. Specific handoff protocols merit evaluation and training to ensure consistent practices in different ICU models and at different times.

Background: Arterial shunting is a well-described method to control hemorrhage and rapidly reestablish flow, but optimal shunt dwell times remain controversial. We hypothesized that prolonged shunt dwell times of more than 6 hours are related to adverse outcomes after major arterial injury., Methods: A review (2005-2013) of all patients with arterial shunts placed after traumatic injury at our urban Level I trauma center was undertaken. Patients who died prior to shunt removal (n = 7) were excluded. Shunt complications were defined as dislodgement, thrombosis, and distal ischemia. Patients were compared on the basis of shunt complications with respect to clinical parameters., Results: The 42 patients who underwent arterial shunting after major vascular injury were primarily young (median, 26 years; interquartile range [IQR], 22-31 years) males (97.6%), severely injured (Injury Severity Score, 17.5 [IQR, 14-29]; shunted vessel Abbreviated Injury Scale score, 4 [IQR, 3-4]) by gunshot (85.7%) requiring neck/torso (33.3%) or upper-extremity (19.1%) or lower-extremity (47.6%) shunts. Thirty-five patients survived until shunt removal, and 5 (14.3%) of 35 developed shunt complications. Demographics and clinical characteristics were compared between those with shunt dwell times of less than 6 hours (n = 19) and more than 6 hours (n = 16). While patients appeared to have a greater injury burden overall in the group with dwell times of more than 6 hours, there were no statistical differences between groups with respect to age, gender, initial systolic blood pressure or hemodynamics during the shunt dwell period, use of vasopressors, Abbreviated Injury Scale score of the shunted vessel, Injury Severity Score, or outcomes including limb amputation or mortality. No patients (0/19) with shunt dwell times of less than 6 hours developed complications, whereas 5 (31.3%) of 16 patients with dwell times of more than 6 hours developed shunt complications (p = 0.05)., Conclusions: In this civilian series, 14% of patients with arterial shunts developed shunt complications. Our data suggest that limiting shunt dwell times to less than 6 hours when clinically feasible may decrease adverse outcomes., Level of Evidence: Therapeutic/care management study, level IV.

Wildland firefighting exposes personnel to combinations of occupational and environmental stressors that include physical activity, heat and sleep restriction. However, the effects of these stressors on sleep have rarely been studied in the laboratory, and direct comparisons to field scenarios remain problematic. The aim of this study was to examine firefighters' sleep during a three-day, four-night simulated wildfire suppression that included sleep restriction and physical activity circuits representative of firefighting wildfire suppression tasks in varied temperatures. Sixty-one volunteer firefighters (37.5±14.5 years of age, mean±SD) were assigned to one of three conditions: control (n=25; 8h sleep opportunities and 18-20°C), awake (n=25; 4h sleep opportunities and 18-20°C) or awake/hot (n=11; 4h sleep opportunities and 33-35°C during the day and 23-25°C during the night). Results demonstrated that amounts of N1, N2 and R sleep, TST, SOL and WASO declined, whilst sleep efficiency increased significantly in the awake and awake/hot conditions compared to the control condition. Results also demonstrated that SWS sleep remained relatively stable in the awake and awake/hot conditions compared to control values. Most importantly, no significant differences were found for any of the sleep measures between the awake and awake/hot conditions. Thus, working in hot daytime temperatures in combination with sleep restriction during the night did not affect patterns of sleep compared to working in temperate conditions in combination with sleep restriction during the night. However, the effects on sleep of high (>25°C) night-time temperatures with sleep restriction in addition to physical activity remains to be studied., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The study evaluated the physical,mental, and functional outcomes following below-the-knee amputation (BKA) for management of chronic, debilitating lower extremity pain. The hypothesis was that patients who undergo a BKA to alleviate chronic pain achieve a greater level of function, experience decreased pain, and benefit from improved health-related quality of life. Patients who received a BKA attended an orthopaedic clinic and completed questionnaires examining their overall health, functional status, mental health, and pain. Thirty-seven patients were identified as eligible for study participation; 15 agreed to participate. Although most participants continued to experience pain in their residual limb after BKA, they reported their pain decreased to a manageable level. Participants experienced a statistically significant improvement in their perceived physical health. The authors believe a BKA for chronic pain is a reasonable treatment option for patients who continue to experience lower extremity pain after failed medical and surgical management of chronic pain. (Journal of Surgical Orthopaedic Advances 26(4):200-205, 2017).

Background and Purpose: Complex regional pain syndrome (CRPS) is a challenging complication after surgery or trauma. This study sought to determine the incidence of CRPS after a second inciting event in a previously unaffected extremity in patients with a history of an ongoing CRPS diagnosis in another extremity., Methods: A retrospective review identified patients with CRPS seen in clinic over a 20-month period. The incidence of CRPS after subsequent surgery or injury in a previous unaffected extremity was determined and compared to an average incidence reported in the literature., Results: Ninety-three patients had a diagnosis of primary CRPS. Nineteen (20.4%) developed CRPS in one or more additional extremity compared to the incidence of 23.4 per 100,000 (0.0234%) in the literature (odds ratio 1069.6, p<0.0001, 95% CI 562.0-2035.7). Twenty patients had a documented secondary injury or surgery in a second extremity. Fifteen (75%) developed secondary CRPS compared to a CRPS incidence rate of 6.4% following distal radius fracture, as determined by literature review (odds ratio 11.7, p<0.001, 95% CI 5.9-23.2)., Conclusions: These result suggest that patients with a history of CRPS are more likely to develop secondary CRPS compared to the rates reported in the literature among the general population., Implications: Patients with a history of CRPS should be counselled that they may be at risk for developing secondary CRPS if they undergo surgery or sustain trauma to another extremity., (Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: We evaluated coronary angiography use among patients with coronary stents suffering postoperative myocardial infarction (MI) and the association with mortality., Methods: Patients with prior coronary stenting who underwent inpatient noncardiac surgery in Veterans Affairs hospitals between 2000 and 2012 and experienced postoperative MI were identified. Predictors of 30-day post-MI mortality were evaluated., Results: Following 12,096 operations, 353 (2.9%) patients had postoperative MI and 58 (16.4%) died. Post-MI coronary angiography was performed in 103 (29.2%) patients. Coronary angiography was not associated with 30-day mortality (odds ratio [OR]: .70, 95% CI: .35-1.42). Instead, 30-day mortality was predicted by revised cardiac risk index ≥3 (OR 1.91, 95% CI: 1.04-3.50) and prior bare metal stent (OR 2.12, 95% CI: 1.04-4.33)., Conclusions: Less than one-third of patients with coronary stents suffering postoperative MI underwent coronary angiography. Significant predictors of mortality were higher revised cardiac risk index and prior bare metal stent. These findings highlight the importance of comorbidities in predicting mortality following postoperative MI., (Published by Elsevier Inc.)

Surprisingly little information is available about the behavior of newborn mammals in the functionally vital context of suckling. We have previously reported notable differences in the pattern of nipple use by kittens of the domestic cat and puppies of the domestic dog. Whereas kittens rapidly develop a "teat order," with each individual using principally 1 or 2 particular nipples, puppies show no such pattern. We asked whether the more "chaotic" behavior seen in puppies of the domestic dog (Canis familiaris) could be the result of relaxed selection due to domestication. In a first test of this hypothesis, we studied suckling behavior in 4 litters of wild-type captive dingoes (Canis dingo), a canid species that has inhabited the Australian mainland in substantial numbers for at least 5,000 years with minimal human influence. On all measures of individual puppies' behavior-time spent attached to nipples, lack of individual use of particular nipples and consequent absence of a teat order, lack of synchronized suckling with other littermates, lack of agonistic behavior-we found no differences between the 2 species. In conclusion, we suggest that the difference between the pattern of suckling behavior of kittens of the domestic cat (and other felids) and the domestic dog is not an artifact of domestication, but rather reflects phylogenetic differences between felids and canids as a consequence of their different lifestyles and associated patterns of parental care. These findings emphasize the need for comparative studies to avoid simplistic generalizations from 1 or 2 species across broad taxonomic groups. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Objective: Unicompartmental knee arthroplasty (UKA) revision is usually due to the degenerative degree of knee articular osteochondral tissue in the untreated compartment. However, it is difficult to simulate the biomechanical behavior on this tissue accurately. This study presents and validates a reliable system to predict which osteoarthritis (OA) patients may suffer revision as a result of biomechanical reasons after having UKA., Design: We collected all revision cases available (n = 11) and randomly selected 67 UKA cases to keep the revision prevalence of almost 14%. All these 78 cases have been followed at least 2 years. An elastic model is designed to characterize the biomechanical behavior of the articular osteochondral tissue for each patient. After calculated the force on the tissue, finite element method (FEM) is applied to calculating the strain of each tissue node. Kernel Ridge Regression (KRR) method is used to model the relationship between the strain information and the risk of revision. Therefore, the risk of UKA revision can be predicted by this integrated model., Results: Leave-one-out (LOO) cross-validation (CV) is implemented to assess the prediction accuracy. As a result, the mean prediction accuracy is 93.58% for all these cases, demonstrating the high value of this model as a decision-making assistant for surgical plaining of knee OA., Conclusions: The results of this study demonstrated that this integrated model can predict the risk of UKA revision with theoretically high accuracy. It combines bio-mechanical and statistical learning approach to create a surgical planning tool which may support clinical decision in the future., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Range of motion (ROM) is important for functional outcome after total knee arthroplasty (TKA); however, some patients hesitate to maximize their ROM postoperatively. The Tampa Scale of Kinesiophobia (TSK) measures patients' fear of movement. The primary purpose of this investigation was to determine whether TSK scores correlated with decreased ROM after primary TKA. A secondary purpose was to determine whether biofeedback could increase ROM after TKA., Methods: Patients were recruited from the senior author's practice between June 2011 and March 2013. A clinical photograph was taken of each patient's knee in maximum passive flexion in the operating room immediately following closure. Patients were randomized to the control or photograph group before incision. A linear mixed model was implemented to determine whether the TSK score and viewing the photo correlated to ROM., Results: Seventy-nine patients were analyzed for correlation between the TSK score and the knee ROM. Sixty patients were analyzed for correlation between viewing the clinical photograph and the knee ROM. The linear mixed model demonstrated a significant negative correlation between the TSK score and both active (β = -0.47, P < .01) and passive (β = -0.66, P < .001) knee flexions. There was a trend toward decreased knee flexion among patients shown their clinical photograph., Conclusion: The TSK was developed as a tool to identify patients at risk for maladaptive responses to painful stimuli. Our data suggest that the TSK may help arthroplasty surgeons identify patients at risk for decreased ROM after TKA. Showing patients a clinical photograph failed to increase ROM after TKA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes following transfer of the supinator motor branch of the radial nerve (SMB) to the posterior interosseous nerve (PIN) and the pronator teres motor branch of median (PTMB) to the anterior interosseous nerve (AIN) in patients with lower brachial plexus injuries., Methods: Since December 2010, 4 patients have undergone combined transfer of the SMB to PIN and PTMB to AIN for lower brachial plexus palsies. The study was prospectively designed, and the patients were followed for 4 years to monitor their functional improvement., Results: One patient failed to return after his 4-month postoperative visit. The other 3 patients all regained M4 thumb and finger extension, and 2 recovered M4 thumb and finger flexion at the final evaluation, a mean 30 months after the nerve transfer surgeries., Conclusions: Combined transfer of the SMB to PIN and PTMB to AIN may lead to successful recovery of digital extrinsic flexion and extension in lower brachial plexus injuries., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Adequate sleep is fundamental to workplace performance. For volunteer firefighters who work in safety critical roles, poor performance at work can be life threatening. Extended shifts and sleeping conditions negatively impact sleep during multi-day fire suppression campaigns. Having sleep disordered breathing (SDB) could contribute further to sleep deficits. Our aim was to investigate whether those with suspected SDB slept and performed more poorly during a fire ground simulation involving sleep restriction. Participants, n = 20 participated in a 3-day-4-night fire ground simulation. Based on oximetry desaturation index data collected during their participation, participants were retrospectively allocated to either a SDB (n = 8) or a non-SDB group (n = 12). The simulation began with an 8 h Baseline sleep (BL) followed by two nights of restricted (4 h) sleep and an 8 h recovery sleep (R). All sleeps were recorded using a standard electroencephalography (EEG) montage as well as oxygen saturation. During the day, participants completed neurobehavioral (response time, lapses and subjective fatigue) tasks. Mixed effects ANOVA were used to compare differences in sleep and wake variables. Analyses revealed a main effect of group for Total sleep (TST), REM , wake after sleep onset (WASO) and Arousals/h with the SDB group obtaining less TST and REM and greater WASO and Arousals/h. The group × night interaction was significant for N3 with the SDB group obtaining 42 min less during BL. There was a significant main effect of day for RRT, lapses and subjective fatigue and a significant day × group interaction for RRT. Overall, the SDB group slept less, experienced more disturbed sleep and had poorer response time performance, which was exacerbated by the second night of sleep restriction. This could present a safety concern, particularly during longer campaigns and is worthy of further investigation. In addition, we would recommend promotion of awareness of SDB, its symptoms and potential impact among volunteers and relevant agencies.

Under controlled laboratory conditions, neurobehavioral assays such as the Psychomotor Vigilance Task (PVT) are sensitive to increasing levels of fatigue, and in general, tend to correlate with subjective ratings. However, laboratory studies specifically curtail physical activity, potentially limiting the applicability of such findings to field settings that involve physical work. In addition, laboratory studies typically involve healthy young male participants that are not always representative of a typical working population. In order to determine whether these findings extend to field-like conditions, we put 88 Australian volunteer firefighters through a multi-day firefighting simulation. Participants were required to perform real-world physical and cognitive tasks under conditions of elevated temperature and moderate sleep restriction. We aimed to examine changes in fatigue in an effort to determine the optimum objective and subjective measures. Objective and subjective tests were sensitive to fatigue outside laboratory conditions. The PVT was the most sensitive assay of objective fatigue, with the Samn-Perelli fatigue scale the most sensitive of the subjective measures. The Samn-Perilli fatigue scale correlated best with PVT performance, but explained a small amount of variance. Although the Samn-Perelli scale can be easily administered in the field, the wide range of individual variance limits its efficacy as a once-off assessment tool. Rather, fatigue measures should be applied as a component of a broader fatigue risk management system. Findings provide firefighting agencies, and other occupations involving physical work, guidance as to the most sensitive and specific measures for assessing fatigue in their personnel.

Background: Dynamic knee valgus in females has been associated with various knee pathologies. Abnormal 3D hip and knee kinematics contribute prominently to this presentation, and these may become more aberrant with more demanding tasks. Underlying genu valgus may also accentuate such kinematics, but this effect has never been tested. Therefore, the purpose of this study was to compare 3D hip and knee kinematics during walking, running, and single-limb drop landing in females with and without genu valgus malalignment. We expected abnormal kinematics to become more evident in the valgus subjects as task demands increased., Methods: Eighteen healthy females with genu valgum and 18 female controls with normal alignment underwent 3D motion analysis while performing walking, running, and single-limb drop-landing trials. Sagittal, frontal, and transverse plane hip and knee kinematics were compared between groups across tasks using analyses of variance and between-group effect sizes., Findings: Group differences did not generally increase with higher forces. The valgus females demonstrated decreased hip flexion (ES=0.72-0.88) and increased knee abduction (ES=0.87-1.47) across the tasks. During running and single-limb drop landing, they showed increased knee external rotation (ES=0.69-0.73). Finally, during walking, the valgus females showed increased hip adduction (ES=0.69)., Interpretation: These results suggest that females with genu valgus alignment utilize aberrant hip and knee mechanics previously associated with dynamic valgus in the literature, but that these pathomechanics do not generally worsen with rising task demands. Healthy females that present with genu valgus may be natively at elevated risk for knee pathology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: Autologous nerve grafting remains the gold standard for repair of peripheral nerve injuries. Its use, however, is limited by donor nerve availability and donor site morbidity. This is especially problematic after failure of an initial autograft that requires a repeat nerve graft, resulting in a second surgical site with associated morbidity. Based on the molecular differences in nerve degeneration in the proximal and distal segments after transection, we hypothesized that a chronically-denervated proximal stump may be viable for autologous nerve repair., Methods: 20 Sprague-Dawley rats underwent right sciatic nerve excision and sural nerve transection. After 8 weeks, nerve repair was performed by harvesting the proximal segment of the sural nerve (n=10) or a fresh sural nerve (n=10) from the contralateral hind limb. Electrophysiological changes were analyzed to compare the fresh and denervated grafts., Results: Electrophysiological testing demonstrated higher compound motor action potential in the denervated group compared to the fresh autograft group, however this difference was not statistically significant (p=0.117)., Conclusion: The proximal segment of a chronically-denervated sural nerve can be as effective as a fresh sural nerve for autologous repair of peripheral nerve injuries in a rodent model., Competing Interests: Conflict of interest statement The authors have no conflicts of interest to declare.

Therapeutic agents that block the calcitonin gene-related peptide (CGRP) signaling pathway are a highly anticipated and promising new drug class for migraine therapy, especially after reports that small-molecule CGRP-receptor antagonists are efficacious for both acute migraine treatment and migraine prevention. Using XenoMouse technology, we successfully generated AMG 334, a fully human monoclonal antibody against the CGRP receptor. Here we show that AMG 334 competes with [(125)I]-CGRP binding to the human CGRP receptor, with a Ki of 0.02 nM. AMG 334 fully inhibited CGRP-stimulated cAMP production with an IC50 of 2.3 nM in cell-based functional assays (human CGRP receptor) and was 5000-fold more selective for the CGRP receptor than other human calcitonin family receptors, including adrenomedullin, calcitonin, and amylin receptors. The potency of AMG 334 at the cynomolgus monkey (cyno) CGRP receptor was similar to that at the human receptor, with an IC50 of 5.7 nM, but its potency at dog, rabbit, and rat receptors was significantly reduced (>5000-fold). Therefore, in vivo target coverage of AMG 334 was assessed in cynos using the capsaicin-induced increase in dermal blood flow model. AMG 334 dose-dependently prevented capsaicin-induced increases in dermal blood flow on days 2 and 4 postdosing. These results indicate AMG 334 is a potent, selective, full antagonist of the CGRP receptor and show in vivo dose-dependent target coverage in cynos. AMG 334 is currently in clinical development for the prevention of migraine., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Postoperative pain control following total joint arthroplasty results in improved patient mobilization, participation in physical therapy, and potentially reduced hospital costs. It was hypothesized that using a multimodal pain protocol focusing on periarticular injections including liposomal bupivacaine would have improved results when compared with a parenteral opioid-based regimen. The results showed a decrease in length of stay and rate of discharge to skilled nursing facilities with the implementation of a novel multimodal pain protocol. Furthermore, there was no change in patient satisfaction before and after the execution of the new protocol. It was concluded that using a multimodal pain protocol based on periarticular injections can lead to decreased length of stay and a decrease in transfer to skilled nursing facilities without a change in patient satisfaction.

Background: Trauma research has been limited by perceived patient reluctance to participate in exception from informed consent (EFIC) studies. We hypothesized that race, socioeconomic status, and proximity to violence influence willingness to participate in and perception of EFIC research among at-risk populations., Methods: Trauma patients, families, and community members ranked statements regarding attitude toward EFIC in the context of an upcoming trial and willingness to participate in emergency research using a 5-point Likert scale during a community consultation. Higher total scores reflected a more positive attitude regarding EFIC (range, 6-30; neutral, 18) and willingness (range, 23-115; neutral, 69). Subject zip code was used to calculate median income, as an estimate for socioeconomic status, and proximity to the five most violent city zip codes. Linear regression, Spearman's correlation, and Kruskal-Wallis tests (p < 0.05) were used to evaluate relationships between estimated socioeconomic status, race, mechanism of injury, proximity to violence, and attitudes toward EFIC., Results: A total of 179 subjects participated including trauma patients (n = 99), families (n = 33), and community members (n = 47). Overall, participants were supportive of EFIC and reported high scores in willingness to participate (median, 24; interquartile range, 21-25; median 89, interquartile range, 82-95, respectively). Proximity to violence did correlate with race (p = 0.03) but was not associated with violent mechanism of injury, perception of EFIC, or willingness to participate in emergency research. Estimated socioeconomic status and race did not correlate with perception of or willingness to participate in EFIC., Conclusion: Based on our data, there is no correlation between either proximity to violence or estimated socioeconomic status and willingness to participate in EFIC research. Given this lack of correlation, researchers should partner with at-risk communities to conduct EFIC studies without concern for limited participation., Level of Evidence: Epidemiologic/prognostic study, level III.

Background: The Injury Severity Score (ISS) has been validated in numerous studies and has become one of the most common trauma scoring systems since its inception. The ISS equation was later modified to create the New Injury Severity Score (NISS). By using the three most severe injuries regardless of body region, the NISS seems well suited to describe patients of penetrating trauma, where injuries often cluster within a single body region. We hypothesized that NISS would better predict outcomes than ISS in penetrating trauma patients., Methods: An analysis (June 2008 to March 2009) of all severely injured (length of hospital stay ≥ 48 hours, intensive care unit admission, interhospital transfer, or death) penetrating trauma patients revealed final study sample of 256 patients. ISS and NISS were compared as predictors for both mortality and complications through area under the receiver operating characteristic curve, Hanley-McNeil test, multiple-variable logistic regression, and Hosmer-Lemeshow goodness-of-fit test analysis., Results: Of 256 study patients, 195 (76.2%) survived until discharge. The mean (ISS, 21.7 ± 21.1 vs. NISS, 27.4 ± 22.0; p < 0.001) and median (ISS, 14.0 vs. NISS, 21.0) ISS was lower than those of the NISS. Overall, 173 patients (67.6%) had discordant scores with 26% and 43% having scores greater than 25 (ISS and NISS, respectively, p < 0.01). The mortality area under the curve (AUC) for NISS was greater than the AUC for ISS in all penetrating patients (0.930 vs. 0.885, p = 0.008), those with penetrating torso injuries (NISS, 0.934 vs. ISS, 0.881, p < 0.001), and those with severe (score > 25) injuries (NISS, 0.845 vs. ISS, 0.761, p < 0.001). In patients surviving for more than 48 hours, the complications AUC for NISS was also greater than the AUC for ISS (NISS, 0.838 vs. ISS, 0.784; p = 0.023)., Conclusion: The NISS outperformed ISS as a predictor of both mortality and complications in civilian penetrating trauma patients. These results indicate that NISS is a superior scoring system for patients with penetrating injuries., Level of Evidence: Prognostic study, level III.

Purpose: To compare minimally invasive intramedullary nails (IMN) and volar locking plates (VLP) for the treatment of unstable distal radius fractures by evaluating postoperative subjective, radiographic, and functional outcomes. The hypothesis was that IMN patients would have less pain and required less pain medication in the early postoperative period and returned to work earlier than VLP patients., Methods: Sixty patients with closed, displaced, unstable, extra-articular, metaphyseal fractures of the distal radius were randomized to receive a VLP or an IMN for internal fixation. Functional outcomes (Quick Disabilities of the Arm, Shoulder, and Hand, Michigan Hand Questionnaire), radiographic measurements (ulnar variance, radial height, inclination, and volar tilt), and range of motion were assessed until final follow-up at 2 years after surgery. Narcotic pain medication use was documented for 5 weeks following surgery., Results: There were 2 groups of 30 patients with IMN (mean age, 55 ± 14 y) or VLP (mean age, 55 ± 16 y) with similar demographics and comorbidities. Patients with IMN regained extension earlier but had similar range of motion to patients with VLP at final follow-up. There was similar improvement in Michigan Hand Questionnaire, Quick Disabilities of the Arm, Shoulder, and Hand, and strength between groups. Five weeks after surgery, fewer IMN patients required narcotic pain medication (13%) than VLP patients (33%). Radiographic outcomes were similar at final follow-up. There were 3 failures with IMN versus 1 failure with VLP. All 10 employed patients with IMN returned to previous work compared with 10 of the 12 employed patients with VLP. Time to return to work was similar for both groups., Conclusions: In a cohort of similar patients, IMN and VLP provided comparable improvement in functional and radiographic outcomes. Patients with IMN required less narcotic pain medication after surgery than VLP patients., Type of Study/level of Evidence: Therapeutic II., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the 5-year survival rate of patients on dialysis requiring an upper extremity amputation with those who did not require such surgery and to analyze whether such an amputation was prognostic for mortality., Methods: The medical records of 20 consecutive patients with end-stage renal disease who received upper extremity amputations were reviewed. Control patients (n = 40) were matched based on age, sex, and duration of dialysis treatment. A Kaplan-Meier survival analysis was performed., Results: The mean survival time after the index surgery for the surgical group was 4.95 years ± 0.90 years, and the mean survival for the control group was 8.40 years ± 0.61 years. The probability of death (the event) was statistically greater in the surgical group. The overall 5-year survival rates for the surgical and the nonsurgical groups were 35% (7 of 20) and 70% (28 of 40), respectively. Patients with diabetes in the surgical group had a significantly lower 5-year survival rate, a greater number of amputations, and a greater number of wound-healing failures., Conclusions: The 5-year survival rate from the index surgery of the surgical group was half that of the nonsurgical group. Increased mortality may be partially attributed to the poor vascular health of the patient. This analysis may help the hand surgeon to more effectively counsel patients with end-stage renal disease about the prognosis associated with an upper extremity amputation and, more importantly, supports the goal of timely intervention by the multidisciplinary team to optimize care planning and to improve surgical outcomes and quality of life., Type of Study/level of Evidence: Prognostic III., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Objective: Limited evidence exists to guide clinical management of acute finger ischemia (AFI). To further inform diagnostic evaluation and decision making, we evaluated anatomic findings, procedural management, and amputation-free survival in an institutional cohort of patients with AFI., Methods: Consecutive patients undergoing transfemoral upper extremity angiography for AFI were identified. Clinical, laboratory, and procedural data were collected retrospectively from medical records, and arteriograms were reviewed to characterize anatomic findings. Telephone interviews were used to determine long-term outcomes, and additional symptomatic assessments (Symptom Severity and Functional Status scale, the Cold Sensitivity Severity scale, and the McGill Pain Severity Scale) were available in a subgroup of patients. Outcomes included anatomic findings, use of thrombolysis, complications, and amputation-free survival. Descriptive statistics and survival analysis were used to evaluate results., Results: Thirty-five patients (54% women) were analyzed with a median follow-up of 13.7 months. Symptom duration at time of presentation ranged from 1 to 28 days, and seven patients had tissue loss or gangrene, or both. Mean age was 47.7 ± 12.2 years. Baseline characteristics included smoking in 22 (65%), connective tissue disorder in 11 (31%), and history of repetitive hand trauma in 10 (29%). The most frequent anatomic location of arterial pathology identified during angiography was distal to the wrist (n = 32), including eight ulnar/radial aneurysms; upper arm (n = 3) and forearm (n = 8) lesions were less common. Sixteen patients were treated with catheter-directed thrombolysis, of which eight (50%) had interval anatomic improvement on repeat angiography. Procedure-related adverse events associated with angiography included bleeding (n = 3) and pseudoaneurysm (n = 1). Eleven of 35 patients had subsequent surgical revascularization at a median of 15 days after angiography. Estimated (standard error) amputation-free survival was 0.88 (0.07) at 1 month and 0.84 (0.08) at 6 months among patients without tissue loss or gangrene. Estimated 60-day amputation-free survival was 0.84 (standard error, 0.08). Overall amputation-free survival was similar between patients managed with vs without thrombolysis (P = .61), but subgroup analysis of those patients without tissue loss or gangrene at the time of presentation revealed a trend toward improved amputation-free survival with use of thrombolysis, with 60-day amputation-free survival of 0.92 vs 0.75 (P = .12). Persistent late symptoms were present in 17 patients (48.6%) at the last follow-up and were generally characterized as mild by functional and pain scale assessments., Conclusions: Angiography performed for AFI frequently identifies distal occlusive disease, and catheter-directed thrombolysis may expand revascularization options in select patients., (Copyright © 2014 Society for Vascular Surgery. All rights reserved.)

The theme of this month's issue of Clinical Pharmacology & Therapeutics is pharmacometrics. When looking back at the early days of pharmacometrics, current contributions to the drug development process look impressive. The questions are whether the original promise is being kept and how the impact can become even greater.

Background: Early trauma deaths have the potential for salvage with immediate surgery. We studied time from injury to death in this group to qualify characteristics and quantify time to the operating room, yielding the greatest opportunity for salvage., Methods: The Pennsylvania Trauma Outcomes Study (PTOS) is a comprehensive registry including all Pennsylvania trauma centers. PTOS was queried for adult trauma patients from 1999 to 2010 dying within 4 hours of injury. The distribution of time to death (TD) was examined for subgroups according to mechanism of injury, hypotension (defined as systolic blood pressure ≤ 90 mm Hg), and operation required. The 5th percentile (TD5) and the 50th percentile (TD50) were calculated from the distributions and compared using the Mann-Whitney U-test., Results: The PTOS yielded 6,547 deaths within 4 hours of injury. The overall TD5 and TD50 were 0:23 (hour:minute) and 0:59, respectively. Median penetrating injury times were significantly shorter than blunt injury times (TD5/TD50, 0:19/0:43 vs. 0:29/1:10). Median time was significantly shorter for hypotensive versus normotensive patients (TD5/TD50, 0:22/0:52 vs. 0:43/2:18). Operative subgroups had different TD5/TD50 (abdominal surgery [n = 607], 1:07/2:26; thoracic surgery [n = 756] 0:25/1:25; vascular surgery [n = 156], 0:35/2:15; and cranial surgery [n = 18], 1:20/2:42)., Conclusion: Early trauma deaths have the potential for salvage with immediate surgery. We found TD to vary based on mechanism of injury, presence of hypotension, and type of surgery needed. With the use of TD5 and TD50 benchmarks in these subgroups, a trauma system may determine if decreased time to the operating room decreases mortality. Trauma systems can use these data to further improve prehospital and initial hospital phases of care for this subset of early death trauma patients., Level of Evidence: Epidemiologic study, level III.

Analytical techniques were combined with geochemical modelling to study the release mechanisms of pollutants from an abandoned gold mining tailings storage facility near Johannesburg. Inverse modelling of sampled tailings pond water and experimental single extractions using various solutions indicated which combination of naturally occurring leaching solutions were likely to give rise to the observed pond water quality. The potential fate of metals in the pond was predicted by modelling the formation of efflorescent crusts and adsorption onto hydrated iron oxide minerals.