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OBJECTIVE To describe the clinical and epidemiologic features of persons with dog and cat bite injuries who presented to emergency departments. SAMPLE Records of 648,492 dog and cat bite–related emergency department visits in California from 2005 to 2019. PROCEDURES Visits were selected by standardized International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification codes that indicated a bite as an external cause of injury in the medical record. Incidence rates were calculated for patient demographics, location and month of bite incident, characteristics of bite injury, infection, patient outcome/disposition, and expected source of payment. Cross-sectional descriptive analysis was performed. RESULTS The average annual incidence of dog bites was highest in children aged < 10 years and males, while that of cat bites was highest in adults aged ≥ 80 years and females. Bites were more likely to occur in rural settings, in private residences, and during the summer. The median household income for zip codes in which animal bite patients resided was lower than the statewide median household income. Both dog and cat bite injuries were more likely to occur to upper limbs. Bacteria were isolated from 3% of dog bite injuries and 21.5% of cat bite injuries at initial presentation. CLINICAL RELEVANCE Epidemiologic findings about persons presenting to emergency departments for animal bite injuries can inform bite prevention efforts by identifying at-risk populations. Effective animal bite prevention demands an ongoing multisectoral program of veterinarians and other health professionals, collaborating with community and governmental organizations, to develop and implement integrated strategies within the context of other socially contributory factors.

Motor action selection engages a network of frontal and parietal brain regions. After stroke, individuals activate a similar network, however, activation is higher, especially in the contralesional hemisphere. The current study examined the effect of practice on action selection performance and brain activation after stroke. Sixteen individuals with chronic stroke (Upper Extremity Fugl-Meyer motor score range: 18-61) moved a joystick with the more-impaired hand in two conditions: Select (externally cued choice; move right or left based on an abstract rule) and Execute (simple response; move same direction every trial). On Day 1, reaction time (RT) was longer in Select compared to Execute, which corresponded to increased activation primarily in regions in the contralesional action selection network including dorsal premotor, supplementary motor, anterior cingulate and parietal cortices. After 4 days of practice, behavioural performance improved (decreased RT), and only contralesional parietal cortex significantly increased during Select. Higher brain activation on Day 1 in the bilateral action selection network, dorsolateral prefrontal cortex and contralesional sensory cortex predicted better performance on Day 4. Overall, practice led to improved action selection performance and reduced brain activation. Systematic changes in practice conditions may allow the targeting of specific components of the motor network during rehabilitation after stroke.

Background Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise. Methods We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis. Results Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend Conclusions Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.

ONC201/TIC10 is a small-molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway–inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small-molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes, including the multikinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib cotreatment to enhance anticancer responses. Cancer Res; 75(8); 1668–74. ©2015 AACR.

Supplementary Table and Figure Legends. Legends for Supplementary Tables S1-S4 and Supplementary Figures S1-S12.

Supplementary Figures S1-S12. Validation of kinase regulators of ONC201 sensitivity (S1); KSR1 shifts the ONC201, but not lapatinib, dose-response curve downward (S2); KSR1 does not regulate ONC201-induced TRAIL or DR5 (S3); KSR1 does not affect ONC201-mediated inhibition of MAPK or Akt inhibition (S4); Distribution of ONC201 synergy instances by drug (S5); Validation of ONC201 combinatorial activity with approved anti-cancer small molecules (S6); ONC201 synergizes with sorafenib in HepG2 cells (S7); ONC201 and sorafenib cooperatively induce apoptosis, TRAIL, and DR5 in vivo (S8); ONC201 and sorafenib cooperatively induce apoptosis in HepG2 cells (S9); ONC201 and sorafenib combination therapy is well tolerated and effective in vivo (S10); FLIP, Mcl-1, and KSR-1 knockdown enhances ONC201 response in HCT116 cells (S11); Model of ONC201-induced TRAIL signaling and sensitivity factors (S12).

Supplementary Tables S1-S4. Kinase regulators of ONC201 sensitivity (S1); Validation of kinase regulators of ONC201 sensitivity (S2); ONC201 and sorafenib combinatorial activity in HCC and RCC (S3); Combination indices for ONC201 and sorafenib activity (S4).

Mosquitoes transmit a wide variety of devastating pathogens when they bite vertebrate hosts and feed on their blood. However, three entire mosquito genera and many individual species in other genera have evolved a nonbiting life history in which blood is not required to produce eggs. Our long-term goal is to develop novel interventions that reduce or eliminate the biting behavior in vector mosquitoes. A previous study used biting and nonbiting populations of a nonvector mosquito

Amyloidosis is a heterogeneous disease that can cause a wide array of nonspecific symptoms when the gastrointestinal (GI) tract is involved, including weight loss, early satiety, change in bowel habits with diarrhea, constipation, or alternating bowel pattern. Endoscopy with biopsy for Congo red staining establishes the diagnosis and fibril subtyping helps to guide targeted treatment options. Light chain amyloidosis is the most frequent subtype found throughout the GI tract. Transthyretin amyloidosis is most likely to be found on rectal biopsy. Management of the symptoms of GI tract involvement with amyloidosis relate to addressing the underlying symptom complex that is produced and generally abstracted from the management of severe forms of functional GI disorders. Attention to improving symptom management and nutrition status can improve quality of life in these patients.

IntroductionPositive social comparative feedback indicates to the learner that they are performing better than others. While this type feedback supports motor skill learning in some tasks, the effect of social comparative feedback on implicit motor sequence learning remains unknown. The aim of this study was to determine the effect of positive social comparative feedback on the learning of and expectancies for a motor sequence task.MethodsForty-eight individuals practiced a joystick-based sequence task and were divided into three feedback groups: CONTROL (no performance feedback), RT ONLY (response time only feedback), and RT+POS (response time plus positive social comparison). Participants attended sessions on two consecutive days: Day 1 for repetitive motor practice/skill acquisition and Day 2 for retention testing. Performance related expectancies, like perceived competence, were measured before and after motor practice on Day 1 and at retention on Day 2.ResultsWhile all groups improved with practice, the CONTROL group showed better overall performance/learning (faster response times) compared with the RT ONLY group. Despite similar response times, the RT+POS showed higher peak velocities than the RT ONLY group. Overall, the RT+POS and CONTROL demonstrated increases in perceived competence while the RT ONLY group did not.DiscussionThe results of this study suggest that feedback content is an important consideration during motor practice sessions since feedback without context (RT ONLY) may be detrimental to motor sequence learning. The results also suggest that, if providing performance related feedback during practice of a skill that relies on implicit sequence learning processes, comparative context may be necessary for enhancing expectancies and supporting.

Objective Early administration of tranexamic acid (TXA) has been shown to save lives in trauma patients, and some U.S. emergency medical systems (EMS) have begun providing this therapy prehospital. Treatment protocols vary from state to state: Some offer TXA broadly to major trauma patients, others reserve it for patients meeting vital sign criteria, and still others defer TXA entirely pending a hospital evaluation. The purpose of this study is to compare the avoidable mortality achievable under each of these strategies, and to report on the various approaches used by EMS. Methods We used the National Center for Health Statistics Underlying Cause of Death data to identify a TXA-naïve population of trauma patients who died from 2007 to 2012 due to hemorrhage. We estimated the proportion of deaths where the patient was hypotensive or tachycardic using the National Trauma Data Bank. We used avoidable mortality risk ratios from the landmark CRASH 2 study to calculate lives saved had TXA been given within one hour of injury based on a clinician’s gestalt the patient was at risk for significant hemorrhage; had it been reserved only for hypotensive or tachycardic patients; or had it been given between hours one to three of injury, considered here as a surrogate for deferring the question to the receiving hospital. Results Had TXA been given within 1 hour of injury, an average of 3409 deaths per year could have been averted nationally. Had TXA been given between one and three hours after injury, 2236 deaths per year could have been averted. Had TXA only been given to either tachycardic or hypotensive trauma patients, 1371 deaths per year could have been averted. Had TXA only been given to hypotensive trauma patients, 616 deaths per year could have been averted. Similar trends are seen at the individual state level. A review of EMS practices found 15 statewide protocols that allow EMS providers to administer TXA for trauma. Conclusion Providing early TXA to persons at risk of significant hemorrhage has the potential to prevent many deaths from trauma, yet most states do not offer it in statewide prehospital treatment protocols.

Prior research links adaptive humor styles (affiliative and self-enhancing) with enhanced psychological well-being and maladaptive humor styles (aggressive and self-defeating) with worse psychological well-being, primarily through humor styles’ influence on individuals’ social interactions and efforts to positively reframe stressors. The present study examined the unique relation of each humor style with psychological well-being with a focus on understanding mechanisms of adjustment under highly stressful conditions. Ninety-nine parents of children with disabilities were surveyed at the beginning of the COVID-19 pandemic in the United States in March 2020, and 79 parents completed follow-up surveys in July 2020. As predicted, at T1, self-enhancing humor was associated with less psychological distress and greater family satisfaction, self-defeating humor was associated with greater distress, and aggressive humor was associated with lower family satisfaction. Moreover, affiliative humor predicted decreased psychological distress over time, whereas self-defeating humor predicted increased psychological distress and decreased family satisfaction over time. Relations were largely mediated by caregiver positive reappraisal, family efforts to reframe daily disability-related challenges, and negative social interactions. Future research should further examine the influence of caregiver humor styles on family dynamics, family reframing norms, and caregiving efficacy.

Background. Structural integrity of the ipsilesional corticospinal tract (CST) is important for upper limb motor recovery after stroke. However, additional neuromechanisms associated with motor function poststroke are less well understood, especially regarding the lower limb. Objective. To investigate the neural basis of upper/lower limb motor deficits poststroke by correlating measures of motor function with diffusion tensor imaging-derived indices of white matter integrity (fractional anisotropy (FA), mean diffusivity (MD)) in primary and secondary motor tracts/structures. Methods. Forty-three individuals with chronic stroke (time poststroke, 64.4 ± 58.8 months) underwent a comprehensive motor assessment and MRI scanning. Correlation and multiple regression analyses were performed to examine relationships between FA/MD in a priori motor tracts/structures and motor function. Results. FA in the ipsilesional CST and red nucleus (RN) was positively correlated with motor function of both the affected upper and lower limb ( r = 0.36 ‐ 0.55 , p ≤ 0.01 ), while only ipsilesional RN FA was associated with gait speed ( r = 0.50 ). Ipsilesional CST FA explained 37.3% of the variance in grip strength ( p < 0.001 ) and 31.5% of the variance in Arm Motricity Index ( p = 0.004 ). Measures of MD were not predictors of motor performance. Conclusions. Microstructural integrity of the ipsilesional CST is associated with both upper and lower limb motor function poststroke, but appears less important for gait speed. Integrity of the ipsilesional RN was also associated with motor performance, suggesting increased contributions from secondary motor areas may play a role in supporting chronic motor function and could become a target for interventions.

Background and purpose Neurologic physical therapy (PT) can assist people with neurologic conditions and injuries to optimize their health and well-being by addressing barriers at the individual, relationship, community, and societal levels. The purpose of this special interest article is to provide consensus-driven strategies to address barriers to implementing health promotion and wellness (HPW)-related neurologic PT practice. Summary of key points Environmental scan, literature review, and expert input were used to determine barriers and develop strategies. Barriers include lack of time; low knowledge, self-efficacy, and awareness; client complexity; and lack of HPW resources; as well as concerns regarding payment and scope of practice. Four key strategies emerged: (1) develop and disseminate a consensus-based scope of practice for HPW in neurologic PT; (2) increase knowledge of resources related to HPW; (3) promote delivery models for HPW-related neurologic PT; and (4) encourage advocacy, community building and partnership along the continuum of care. Recommendations for clinical practice Clinicians should practice to their full scope of HPW-related PT practice. This includes optimizing movement, including physical activity and fitness, as well as reinforcing the importance of healthy sleep, nutrition, stress, and smoking cessation. These activities address primary, secondary, and tertiary prevention. Clinicians are encouraged to report their experiences with HPW-focused delivery models and outcomes. Additional research is needed to understand the full impact of HPW on PT practice (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A364).

Background Mosquitoes of the Culex pipiens complex are found across the globe and are the focus of many research studies. Among the temperate species C. pipiens sensu stricto (s.s.), two forms are usually described: molestus and pipiens. These two forms are indistinguishable in terms of morphology but show behavioral and physiological differences that may have consequences for their associated epidemiology. The two forms are well defined in the northern part of the species distribution, where autogeny is strictly associated with the molestus form. However, whether the two remain distinct and show the characteristic differences in behavior is less clear in North Africa, at the southern edge of their range. Methods The association between autogeny, as determined by ovarian dissection, and molecular forms, based on the CQ11 microsatellite marker, was studied in six Moroccan populations of C. pipiens. Results An overall low prevalence of autogeny was found at three of the Moroccan regions studied, although it reached 17.5% in the Agadir population. The prevalence of form-specific CQ11 alleles was quite similar across all populations, with the molestus allele being rarer (approx. 15%), except in the Agadir population where it reached 43.3%. We found significant deficits in heterozygotes at the diagnostic CQ11 locus in three populations, but the three other populations showed no significant departure from panmixia, which is in line with the results of a retrospective analysis of the published data. More importantly, we found no association between the autogeny status and CQ11 genotypes, despite the many females analyzed. Conclusions There was limited evidence for two discrete forms in Morocco, where individuals carrying pipiens and molestus alleles breed and mate in the same sites and are equally likely to be capable of autogeny. These observations are discussed in the epidemiological context of Morocco, where C. pipiens is the main vector of several arboviruses. Graphical Abstract

Background Brucellosis is a severe occupational or foodborne zoonosis throughout much of the world. Although eradicated from domestic cattle in the United States, brucellosis remains a disease risk to people through acquisition and consumption of animal products from endemic countries. Methods Cases of human brucellosis reported through the California public health disease surveillance network were reviewed for 1993 to 2017. Results From 1993 to 2017, 492 cases of brucellosis were reported in California residents. Persons aged >65 years represented less than 20% of cases, but incidence in this age group (0.94 cases per 1 000 000 population per year) was more than twice the incidence in persons aged Conclusions This study underscores the continuing serious health threat of brucellosis for Latinos in California, particularly older men, and the need for targeted public health messaging on preventing the risk presented by importation and consumption of unpasteurized dairy products from outside of the United States, principally Mexico.

With a population of forty million and substantial geographic variation in sociodemographics and health services, California is an important setting in which to study disparities. Its population (37.5 percent White, 39.1 percent Latino, 5.3 percent Black, and 14.4 percent Asian) experienced 59,258 COVID-19 deaths through April 14, 2021-the most of any state. We analyzed California's racial/ethnic disparities in COVID-19 exposure risks, testing rates, test positivity, and case rates through October 2020, combining data from 15.4 million SARS-CoV-2 tests with subcounty exposure risk estimates from the American Community Survey. We defined "high-exposure-risk" households as those with one or more essential workers and fewer rooms than inhabitants. Latino people in California are 8.1 times more likely to live in high-exposure-risk households than White people (23.6 percent versus 2.9 percent), are overrepresented in cumulative cases (3,784 versus 1,112 per 100,000 people), and are underrepresented in cumulative testing (35,635 versus 48,930 per 100,000 people). These risks and outcomes were worse for Latino people than for members of other racial/ethnic minority groups. Subcounty disparity analyses can inform targeting of interventions and resources, including community-based testing and vaccine access measures. Tracking COVID-19 disparities and developing equity-focused public health programming that mitigates the effects of systemic racism can help improve health outcomes among California's populations of color.

The goal of this review is to summarize recent evidence linking behavioral risk factors to early-onset colorectal cancer (EO-CRC) as the incidence continues to rise by 2% annually in the USA. The potential mechanisms linking these risk factors to EO-CRC are also discussed. Obesity and sedentary behavior have been associated with an increased risk of EO-CRC in women through a large cohort study, while the data is inconclusive for men. Diabetes was also associated with an increased risk of EO-CRC in a large Swedish cohort study. While the evidence for metabolic syndrome and diet comes from cross-sectional studies, they still point to an association with EO-CRC. The mechanisms underlying these risk factors include inflammation, gut dysbiosis, and aberrant mitogenic signaling. The etiology of EO-CRC likely involves a multifactorial mechanism that will require a multidisciplinary approach. Existing consortia and new data harmonization of multiple studies will be useful in re-evaluating the role of established lifestyle/genetic risk factors of CRC in EO-CRC. Future investigations should prospectively collect information on exposures and biospecimens, particularly during early life, to further elucidate risk factors and contributors to the rising incidence of EO-CRC.

The effects of permethrin (PRM) and deltamethrin (DLM) on acoustic or light prepulse inhibition of the acoustic startle response (ASR) and tactile startle response (TSR) were studied in adult male Sprague Dawley rats. Preliminary studies were conducted to optimize the parameters of light and acoustic prepulse inhibition of ASR and TSR. Once these parameters were set, a new group of rats was administered PRM (0 or 90 mg/kg) or DLM (0 or 25 mg/kg) by gavage in 5 mL/kg corn oil. ASR and TSR were assessed using acoustic or light prepulses 6, 8, and 12 h after PRM and 2, 4, and 6 h after DLM exposure. PRM increased ASR 6 h post-treatment with no interaction with acoustic prepulse levels and with no effect on TSR. When light was used as the prepulse, PRM increased ASR and TSR at 6 h with no interaction with prepulse levels. DLM decreased ASR and TSR on trials without prepulses but not on trials with acoustic prepulses. DLM also decreased ASR when light prepulses were present 4 h post-treatment. A final experiment assessed whether the house light in the test cabinet affected ASR and TSR after PRM or DLM exposure. Rats had increased ASR and TSR when house lights were on compared with when they were off, but lighting did not differentially interact with PRM or DLM. Light and acoustic prepulses of ASR and TSR have different effects depending on the test agent and the test parameters.

Archaeologists have struggled to find meaningful and cost effective ways to analyze and interpret prehistoric quarry sites. Quarry site deposits typically contain large quantities of broken rock fragments that generally lack morphological attributes commonly used for lithic debitage analysis. Remnants of quarry pits often overlap and converge, forming complex cultural landscapes that are difficult to document and understand. Archaeological excavations near Glens Falls, New York, uncovered evidence of prehistoric mine pits, dense layers of chert quarry debris, and intensively battered bedrock surfaces. High resolution mass analysis was used to analyze large quantities of quarry debris. A new classification for prehistoric quarry sites and new models for quarry site development are proposed.

Measuring gait parameters (e.g. speed, cadence, step duration) accurately is invaluable for evaluation during treatment of older adults who struggle with disability onset, disease progression, balance, and injurious falls. Traditionally stopwatches or timing gates are used to measure gait speed in clinical settings, and these are limited to measuring gait speed. Other wearable and non-wearable technologies offer the ability to measure additional gait parameters though patients are known to walk differently with the devices and even tend to slow down before engaging with a non-wearable such as a floor mat. Floor vibrations are a promising option to measuring gait parameters while not being intrusive and not requiring line-of-sight to the patient for measurements. This paper presents methodology for extracting gait parameters using vibrations with comparisons to APDM Wearable Technologies Mobility Lab sensors and stopwatch measurements. Performance is examined across 97 participants for self-selected speed forward, full speed forward, and backwards walks at three different testing sites for a total of 1039 walks. Gait speed vibrations measurements demonstrated excellent reliability with APDM Mobility Lab (ICC: 0.98; 99% CI: 0.01±0.01 m/s) and stopwatch (ICC: 0.97; 99% CI: -0.01±0.01 m/s) measurements. Similar excellent results are reported for cadence, gait cycle duration, step duration, and stride length parameters.

Recent studies suggest that ultra-high dose rates of proton radiation (>40 Gy/s; FLASH) confer less toxicity to exposed healthy tissue and reduce cognitive decline compared with conventional radiation dose rates (~1 Gy/s), but further preclinical data are required to demonstrate this sparing effect. In this study, postnatal day 11 (P11) rats were treated with whole brain irradiation with protons at a total dose of 0, 5, or 8 Gy, comparing a conventional dose rate of 1 Gy/s vs. a FLASH dose rate of 100 Gy/s. Beginning on P64, rats were tested for locomotor activity, acoustic and tactile startle responses (ASR, TSR) with or without prepulses, novel object recognition (NOR; 4-object version), striatal dependent egocentric learning ([configuration A] Cincinnati water maze (CWM-A)), prefrontal dependent working memory (radial water maze (RWM)), hippocampal dependent spatial learning (Morris water maze (MWM)), amygdala dependent conditioned freezing, and the mirror image CWM [configuration B (CWM-B)]. All groups had deficits in the CWM-A procedure. Weight reductions, decreased center ambulation in the open-field, increased latency on day-1 of RWM, and deficits in CWM-B were observed in all irradiated groups, except the 5 Gy FLASH group. ASR and TSR were reduced in the 8 Gy FLASH group and day-2 latencies in the RWM were increased in the FLASH groups compared with controls. There were no effects on prepulse trials of ASR or TSR, NOR, MWM, or conditioned freezing. The results suggest striatal and prefrontal cortex are sensitive regions at P11 to proton irradiation, with reduced toxicity from FLASH at 5 Gy.

Introduction: Interventions aimed at improving arm function after stroke primarily focus on movement execution. Approaches that target a specific motor planning process during training have been suggested but not systematically studied. Action selection (AS), or selection of a motor response, is an important planning process with well described behavioral (planning time) and neural (frontal-parietal network) correlates. The purpose of this study was to determine the feasibility of adding AS demands to task-oriented arm training in individuals post-stroke. Methods: Thirty individuals with chronic stroke (59.3±11.0 years of age; 34.9±35.6 months post-stroke) and mild to moderate motor impairment (Fugl-Meyer motor score: 41.4±14.7) completed 15 sessions of task-oriented arm training that included AS demands through abstract visual cues; cues dictated movement task or movement direction/distance/height. AS difficulty was progressed throughout training. Before and after training, individuals completed a joystick-based AS task during functional MRI. Results: Despite the added planning demand, movement repetitions were high (averaged 190.1±25.4 per session). AS accuracy (correct response selection) averaged more than 90% across sessions, even as AS difficulty increased. AS response times and activation in the AS neural network decreased from pre- to post-training, especially in premotor and prefrontal cortices. Gains were seen in upper extremity function (Action Research Arm Test: Pre: 38.0±16.3; Post: 41.4±15.3) and hand-related quality of life (Stroke Impact Scale Hand Domain: Pre: 47.2±23.7; Post: 61.8±24.1). Conclusions: Overall, it was feasible to add AS demands to functional arm training after stroke. Targeted engagement of the AS neural network through the addition of AS demands to arm training may challenge this component of the motor network in a manner that improves motor planning performance, upper extremity function, and neural resource utilization.

Chloridea subflexa and Chloridea virescens are a pair of closely related noctuid species exhibiting pheromone-based sexual isolation and divergent host plant preferences. We produced a novel Illumina short read C. subflexa genome assembly and an improved C. virescens genome assembly, which offer opportunities to study the genomic basis for evolutionarily important traits in this lepidopteran family with few genomic resources. We then examined the feasibility of reference-assisted assembly, an approach that leverages existing high quality genomic resources for genome improvement in closely related taxa and applied it to our Heliothine genomes. Our work demonstrates that reference-assisted assembly has the potential to enhance contiguity and completeness of existing insect genomic resources with minimal additional laboratory costs. We conclude by discussing both the potential and pitfalls of reference-assisted assembly according to the intended downstream assembly application.

Significance Evolution of resistance to management approaches in agricultural landscapes is common and results in economic losses. Early detection of pest resistance prior to significant crop damage would benefit the agricultural community. It has been hypothesized that new genomic approaches could track molecular signals of emerging resistance and trigger efforts to preempt widespread damage. We tested this hypothesis by quantifying genomic changes in the pest Helicoverpa zea over a 15-y period concurrent with commercialization of transgenic Bacillus thuringiensis–expressing crops and their subsequent loss of efficacy. Our results demonstrate the complex nature of evolution in agricultural ecosystems and provide insight into the potential and pitfalls of using genomic approaches for resistance monitoring., Replacing synthetic insecticides with transgenic crops for pest management has been economically and environmentally beneficial, but these benefits erode as pests evolve resistance. It has been proposed that novel genomic approaches could track molecular signals of emerging resistance to aid in resistance management. To test this, we quantified patterns of genomic change in Helicoverpa zea, a major lepidopteran pest and target of transgenic Bacillus thuringiensis (Bt) crops, between 2002 and 2017 as both Bt crop adoption and resistance increased in North America. Genomic scans of wild H. zea were paired with quantitative trait locus (QTL) analyses and showed the genomic architecture of field-evolved Cry1Ab resistance was polygenic, likely arising from standing genetic variation. Resistance to pyramided Cry1A.105 and Cry2Ab2 toxins was controlled by fewer loci. Of the 11 previously described Bt resistance genes, 9 showed no significant change over time or major effects on resistance. We were unable to rule out a contribution of aminopeptidases (apns), as a cluster of apn genes were found within a Cry-associated QTL. Molecular signals of emerging Bt resistance were detectable as early as 2012 in our samples, and we discuss the potential and pitfalls of whole-genome analysis for resistance monitoring based on our findings. This first study of Bt resistance evolution using whole-genome analysis of field-collected specimens demonstrates the need for a more holistic approach to examining rapid adaptation to novel selection pressures in agricultural ecosystems.

After notification of mosquitoes within federal buildings in Washington, DC, we surveyed belowground levels of nearby parking structures for mosquitoes and standing water in the summer months of 2018 and 2019. Aedes aegypti, Ae. albopictus, and members of the Culex pipiens Assemblage were found. Genotyping revealed pipiens, molestus, and quinquefasciatus ancestry among Cx. pipiens Assemblage mosquitoes, and allele frequency comparisons indicated a stable, resident population. Winter and spring aboveground temperatures ranged from −11°C to 35°C, while belowground temperatures never dropped below 5°C or exceeded 30°C, and winter temperatures were significantly higher belowground compared with aboveground. Moderated winter conditions suggest that belowground urban structures could act as refugia for warmer-climate species, like Ae. aegypti and Cx. quinquefasciatus, allowing them to overcome assumed thermal barriers. Surveys of parking structures should be incorporated into integrated vector management programs in urban areas.

Vector-borne pathogens cause many human infectious diseases and are responsible for high mortality and morbidity throughout the world. They can also cause livestock epidemics with dramatic social and economic consequences. Due to its high costs, vector-borne disease surveillance is often limited to current threats, and the investigation of emerging pathogens typically occurs after the reports of clinical cases. Here, we use high-throughput sequencing to detect and identify a wide range of parasites and viruses carried by mosquitoes from Cambodia, Guinea, Mali and the USA. We apply this approach to individual Anopheles mosquitoes as well as pools of mosquitoes captured in traps; and compare the outcomes of this assay when applied to DNA or RNA. We identified known human and animal pathogens and mosquito parasites belonging to a wide range of taxa, as well as DNA sequences from previously uncharacterized organisms. Our results also revealed that analysis of the content of an entire trap could be an efficient approach to monitor and identify rare vector-borne pathogens in large surveillance studies. Overall, we describe a high-throughput and easy-to-customize assay to screen for a wide range of pathogens and efficiently complement current vector-borne disease surveillance approaches., Summary: We describe a surveillance technique enabling the detection of known and previously uncharacterized pathogens present in mosquitoes. This approach could reduce the costs of vector-borne disease monitoring and provide early warning of emerging diseases.

AIMS Ageing-in-place for older people could be more feasible with the support of smart home technology. Ageing in-place may maximize the independence of older adults and enhance their well-being and quality of life, while decreasing the financial burden of residential care costs, and addressing workforce shortages. However, the uptake of smart home technology is very low among older adults. Accordingly, the aim of this study was to explore factors influencing community-dwelling older adults' readiness to adopt smart home technology. DESIGN A qualitative exploratory study design was utilized. METHODS Descriptive data were collected between 2019 and 2020 to provide context of sample characteristics for community-dwelling older adults aged ≥65 years. Qualitative data were collected via semi-structured interviews and focus groups, to generate an understanding of older adult's perspectives. Thematic analysis of interviews and focus group transcripts was completed. The Elderadopt model was the conceptual framework used in the analysis of the findings. RESULTS Several factors influenced community-dwelling older adults' (N = 19) readiness to adopt smart home technology. Five qualitative themes were identified: knowledge, health and safety, independence, security and cost. CONCLUSION Community-dwelling older adults were open to adopting smart home technology to support independence despite some concerns about security and loss of privacy. Opportunities to share information about smart home technology need to be increased to promote awareness and discussion. IMPACT Wider adoption of smart home technology globally into the model of aged care can have positive impacts on caregiver burden, clinical workforce, health care utilization and health care economics. Nurses, as the main providers of healthcare in this sector need to be knowledgeable about the options available and be able to provide information and respond to questions know about ageing-in-place technologies to best support older adults and their families.

Culex pipiens form pipiens and Cx. pipiens form molestus differ in their ability to produce eggs without a bloodmeal. Autogenous mosquitoes, such as the molestus bioform of Cx. pipiens, depend on nutrition acquired as larvae instead of a bloodmeal to fuel the energy intensive process of vitellogenesis, which requires abundant production of yolk proteins. In anautogenous mosquito systems, ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs) transduce nutritional signals and trigger egg maturation in response to a bloodmeal. It is unclear to what extent the process is conserved in autogenous mosquitoes and how the bloodmeal trigger has been replaced by teneral reserves. Here, we measured the effects of a series of nutritional regimens on autogeny, time to pupation, and survival in Cx. pipiens form molestus and form pipiens. We find that abundant nutrients never result in autogenous form pipiens and extremely poor food availability rarely eliminates autogeny from form molestus. However, the number of autogenous eggs generated increases with nutrient availability. Similarly, using qPCR to quantify gene expression, we find several differences in the expression levels of ilps between bioforms that are reduced and delayed by poor nutrition, but not extinguished. Changes in OEH expression do not explain bioform-specific differences in autogeny. Surprisingly, the source of most of the gene expression differences correlated with autogeny is the abdomen, not the brain. Overall, our results suggest that autogeny is modulated by nutritional availability, but the trait is encoded by genetic differences between forms and these impact the expression of ILPs.

ObjectiveEarly-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified.DesignWe conducted a claims-based nested case-control study using IBM® MarketScan® Commercial Database (2006-2015). Incident early-onset CRC diagnosed at ages 18-49 were identified by ICD-9-CM diagnosis code, and the first coded diagnostic pathology date was assigned as the index date. Controls were frequency matched with cases. Type 2 diabetes, stratified by severity, was identified through ICD-9-CM using the Klabunde algorithm. Multivariate logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (Cls).ResultsA total of 6001 early-onset CRC and 52104 controls were included. Type 2 diabetes was associated with an increased risk of early-onset CRC (5.0% in cases vs. 3.7% in controls; OR 1.24; 95% CI 1.09 to 1.41). The positive association was more pronounced for uncontrolled (OR 1.37; 95% CI 1.12 to 1.67) or complicated (OR 1.59; 95% CI 1.08-2.35) type 2 diabetes compared to controlled diabetes (OR 1.13; 95% CI 0.94 to 1.36). The positive association was driven by proximal (OR 1.35; 95% CI 1.03 to 1.77) and distal (OR 1.67; 95% CI 1.30 to 2.15) colon cancer but not rectal cancer.ConclusionsIndividuals with type 2 diabetes have a higher risk of early-onset CRC, with stronger associations for uncontrolled/complicated diabetes. The rising prevalence of type 2 diabetes among younger adults in the US may partially contribute to the increasing incidence of early-onset CRC.

BACKGROUND AND PURPOSE: Persons with stroke have increased risk for recurrent stroke and other health conditions. Group exercise programs like cardiac rehabilitation might reduce this risk. These programs commonly use the six-minute walk to measure aerobic capacity. However, failure to assess balance or fall risk may compromise safety for persons with stroke. The study aim was to determine the association between the six-minute walk test and fall risk in persons with stroke. METHODS: Cross-sectional analysis measured the association between the six-minute walk test and fall risk in 66 persons with stroke with a mean age of 66 years (SD 12) and median stroke chronicity of 60.9 months (range 6.0–272.1). The six-minute walk test alone and combined with potential co-variates were evaluated using logistic regression. The best fit model was used in Receiver Operating Characteristic analysis. Likelihood ratios and post-test probabilities were calculated. RESULTS: Lower six-minute walk test distance was associated with increased fall risk in logistic regression (p=0.002). The area under the curve for the univariate six-minute walk test model (best fit) was 0.701 (p=0.006). The cutoff for increased fall risk was six-minute walk test < 331.65 meters. The post-test probability of fall risk increased to 74.3% from a pre-test probability of 59.1%. DISCUSSION: The moderate association between fall risk and six-minute walk test suggests that in addition to assessing capacity, the six-minute walk test provides insight into fall risk/balance confidence. CONCLUSION: Using the six-minute walk test cutoff to screen fall risk in community exercise programs may enhance safety for persons with stroke without additional testing required.

Objective: To examine unique relations of three distinct dimensions of desirability of control with psychological and physical well-being and coping. Design: Study 1 (n = 122) surveyed undergraduat...

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor’s residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation.

Caring for America’s aging population is a complex humanitarian issue. The number of older adults is expected to increase to 98.5 million by 2060 with a 295% growth in foreign-born older adults, including Asian immigrants. Most older adults will have one or more chronic conditions and 95% of healthcare costs will be attributed to caring for these conditions. Among Asian Americans, common chronic conditions include respiratory disease, cancer, cardiovascular disease, and pain. The National Institutes of Health, Institute on Aging, and National Science Foundation call for innovative technologies to be developed by multidisciplinary teams to address these concerns. Asian community leaders at Asian Health & Service Center and community members in Oregon identified the use of health-assistive technologies as a priority for potentially reducing stress and improving quality of life for both older adults and their caregivers. The purpose of this article is to introduce nurses and healthcare workers, advocating for the interests of Asian/Pacific Island community members, to the innovative health-assistive smart home. The health-assistive smart home uses artificial intelligence to identify and predict health events. Inclusion of minority persons’ data in the development of artificial intelligence has been generally overlooked. This may result in continued health inequities and is incompatible with the goals of global health. Integration of minority voices while exploring the efficacious use of the health-assistive smart home is of significant value to minority populations. Asian immigrant older adults engaging in smart home research and development will enhance the cultural and technical safety of future devices. Asian families may be particularly interested in smart homes for extending independence because they place an emphasis on collective culture and family-based care. Community engagement of stakeholders and steadfast leadership are needed so that future technologies used in healthcare delivery are both technically and culturally sound. A community-engaged research approach promotes community empowerment that is responsive to community identified priorities and is a good fit for studying adoption of smart home monitoring for health-assistance.

To investigate the association between cardiorespiratory fitness and risk of cardiovascular disease, cancer, and all-cause mortality in men with musculoskeletal conditions.Participants were 12,728 men (mean age 47.0 [9.3] y) with a history of musculoskeletal conditions (including joint pain, low back pain, stiff joints, arthritis, osteoporosis, or gout) and were followed for all-cause mortality to December 31, 2003. Fitness was quantified by maximal treadmill exercise test and was categorized for analysis as low, moderate, and high performance. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals.Overall, the multivariable-adjusted hazard ratios and 95% confidence intervals for mortality across incremental fitness categories were 1.00 (reference), 0.45 (0.30-0.68) and 0.35 (0.22-0.53), linear trend P .01 for all-cause, 0.50 (0.23-1.10) and 0.29 (0.12-0.71), linear trend P = .02 for cardiovascular disease, and 0.38 (0.20-0.74) and 0.40 (0.20-0.80), linear trend P = .01 for cancer mortality.Among men with musculoskeletal conditions, higher fitness is associated with lower risk of death by cardiovascular disease, cancer, or any cause, independent of other risk factors.

Objective Strength training is frequently utilized by physical therapists; however, there has been discussion about whether physical therapists utilize strength training adequately. The purpose of this study was to describe and compare the strength training attitudes, behaviors, and knowledge of physical therapists and physical therapy students and to determine how participant characteristics influenced knowledge scores. Methods An anonymous survey was created in 3 rounds. For round 1, researchers used textbooks to create items assessing demographics, attitudes, behaviors, and knowledge regarding strength training. Rounds 2 and 3 consisted of feedback from 7 content experts until 80% consensus was reached; items were added, removed, or edited based on feedback. The final survey was distributed through social media, list servs, and email targeting physical therapists and students based in the United States. Response frequencies for all items were reported. Overall knowledge scores were calculated by summing correct responses for each item, with a maximum score of 13; scores Results There were 777 physical therapist and 648 student participants. Nearly 90% of therapists and students reported frequently prescribing strength training. Over 48% of therapists felt their professional education did not prepare them to apply strength training (compared with 24% of students), and 68% believed that strength training is inadequately applied in physical therapy (compared with 40% of students). Sixty-two percent of therapists and 55% of students scored ≥70% for knowledge items. Additional strength training education and regular participation in strength training increased the odds of scoring ≥70% on knowledge items. Conclusion Physical therapists and physical therapy students frequently prescribe strength training despite similarly low knowledge scores. To increase knowledge, greater emphasis on strength training in professional education, continuing education, participation in strength training, or all 3 is warranted. Impact Strength training is an important intervention used in physical therapy and must be used appropriately to improve the health of patients. According to these findings, strength training education may not currently be optimal, as demonstrated by low knowledge scores by both therapists and students. Further work is needed to determine how knowledge of strength training relates to patient outcomes and also how best to implement strength training in physical therapy education and practice.

Simple Summary Host preference has profound impacts on the epidemiology of mosquito-borne disease transmission, yet much is still unknown about the molecular basis for these preferences. Here, we examined host preference in the West Nile virus vector, Culex pipiens. We examined human and avian landing rates for eight populations: five originating from above- and three from below-ground breeding and overwintering habitats. While above-ground populations tended to be biased toward avian landing and below-ground populations tended toward human landing, a range of behaviors was observed, consistent with other mosquito species. Patterns of differential expression and splice site variation were measured for one avian- and one human-seeking population as a first step toward identifying genes involved in regulation of blood feeding behaviors as well as differences in host preference. We conclude with a discussion of specific differentially expressed genes and their potential to influence host seeking behaviors of Cx. pipiens females. Abstract Host preferences of Cx. pipiens, a bridge vector for West Nile virus to humans, have the potential to drive pathogen transmission dynamics. Yet much remains unknown about the extent of variation in these preferences and their molecular basis. We conducted host choice assays in a laboratory setting to quantify multi-day human and avian landing rates for Cx. pipiens females. Assayed populations originated from five above-ground and three below-ground breeding and overwintering habitats. All three below-ground populations were biased toward human landings, with rates of human landing ranging from 69–85%. Of the five above-ground populations, four had avian landing rates of >80%, while one landed on the avian host only 44% of the time. Overall response rates and willingness to alternate landing on the human and avian hosts across multiple days of testing also varied by population. For one human- and one avian-preferring population, we examined patterns of differential expression and splice site variation at genes expressed in female heads. We also compared gene expression and splice site variation within human-seeking females in either gravid or host-seeking physiological states to identify genes that may regulate blood feeding behaviors. Overall, we identified genes with metabolic and regulatory function that were differentially expressed in our comparison of gravid and host-seeking females. Differentially expressed genes in our comparison of avian- and human-seeking females were enriched for those involved in sensory perception. We conclude with a discussion of specific sensory genes and their potential influence on the divergent behaviors of avian- and human-seeking Cx. pipiens.

Background Cardiac rehabilitation (CR) is a structured exercise program prevalent in the United States for people with cardiovascular disease that has been shown to increase cardiovascular endurance and improve quality of life. Despite similar cardiovascular risk factors, stroke is not among the covered diagnoses for CR. The purpose of this study was to examine the participant impact of integrating survivors of stroke into the exercise portion of an existing hospital‐based CR program through measures of physical function and other health impacts and through qualitative evaluation of participant perception. Methods and Results Subacute and chronic survivors of stroke were integrated into a standard 12‐week, 3 sessions per week, exercise‐based CR program. A total of 29 began the program, 24 completed the program, and 18 were available for 6‐month follow‐up. Quantitative measures were compared preprogram with postprogram with t ‐test or equivalent, and preprogram with postprogram to 6‐month follow‐up with ANOVA or equivalent. Semistructured interviews were completed with 11 participants postprogram. Exercise‐based CR had significant impacts on cardiovascular endurance preprogram to postprogram, with maintenance at 6‐month follow‐up. The participants improved on the 6‐minute walk test on average by 61.92 m(95% CI, 33.99–89.84 m), and maximum metabolic equivalents improved by a median of 3.6 (interquartile range, 2.35). Five times sit to stand (functional strength) improved preprogram to postprogram by a median of 2.85 s (interquartile range, 4.03 s). Qualitative findings highlight additional health improvements. Most participants (83% [15/18]) reported continued exercise at follow‐up. Conclusions Exercise‐based CR has the potential to improve cardiovascular endurance, health status, and quality of life for survivors of stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03706105.