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The availability of nutrients from mosquito blood meals accelerates the development of Plasmodium falciparum laboratory strains in artificially infected Anopheles gambiae mosquitoes. The impact of multiple blood meals on the number of P. falciparum genotypes developing from polyclonal natural human malaria infections (field-isolates) remains unexplored. Here, we experimentally infect An. gambiae with P. falciparum field-isolates and measure the impact of an additional non-infectious blood meal on parasite development. We also assess parasite genetic diversity at the blood stage level of the parasite in the human host and of the sporozoites in the mosquito. Additional blood meals increase the sporozoite infection prevalence and intensity, but do not substantially affect the genetic diversity of sporozoites in the mosquito. The most abundant parasite genotypes in the human blood were transmitted to mosquitoes, suggesting that there was no preferential selection of specific genotypes. This study underlines the importance of additional mosquito blood meals for the development of parasite field-isolates in the mosquito host. [ABSTRACT FROM AUTHOR]

Entomological evaluations of vector control tools often use human landing catches (HLCs) as a standard measure of a direct human-vector contact. However, some tools have additional characteristics, such as mortality, and HLCS are not sensitive for measuring other effects beyond landing inhibition. Therefore, additional measures may need to be considered when evaluating these tools for public health use. This study has two main aims (1) the evaluate the accuracy of HLCs as a proxy for feeding and (2) to compare the predicted reduction in vectorial capacity when we do and do not consider these additional characteristics. To achieve this, we analyse previously published semi-field data from an experiment which used HLCs and another where mosquitoes were allowed to feed in the presence of different dosages of the volatile pyrethroid spatial repellent, transfluthrin. We compare results for two mathematical models: one which only considers the reduction in feeding effect and one which also considers mortality before and after feeding (using data gathered by the aspiration of mosquitoes after the semi-field feeding/landing period and 24 h survival monitoring). These Bayesian hierarchical models are parameterised using Bayesian inference. We observe that, for susceptible mosquitoes, reduction in landing is underestimated by HLCs. For knockdown resistant mosquitoes the relationship is less clear; with HLCs sometimes appearing to overestimate this characteristic. We find HLCs tend to under-predict the relative reduction in vectorial capacity in susceptible mosquitoes while over-predicting this impact in knockdown-resistant mosquitoes. Models without secondary effects have lower predicted relative reductions in vectorial capacities. Overall, this study highlights the importance of considering additional characteristics to reduction in biting of volatile pyrethroid spatial repellents. We recommend that these are considered when evaluating novel vector control tools. [ABSTRACT FROM AUTHOR]

Introduction: Consumption of a Mediterranean diet (MD) has established health benefits, and the identification of novel biomarkers could enable objective monitoring of dietary pattern adherence. Objectives: The present investigation performed untargeted metabolomics on blood plasma from a controlled study of MD adherence, to identify novel blood-based metabolite biomarkers associated with the MD pattern, and to build a logistic regression model that could be used to characterise MD adherence. Methods: A hundred and thirty-five plasma samples from n = 58 patients collected at different time points were available. Using a 14-point scale MD Score (MDS) subjects were divided into 'high' or 'low' MDS adherence groups and liquid chromatography-mass spectrometry (LC–MS/MS) was applied for analysis. Results: The strongest association with MDS was pectenotoxin 2 seco acid (r = 0.53; ROC = 0.78), a non-toxic marine xenobiotic metabolite. Several lipids were useful biomarkers including eicosapentaenoic acid, the structurally related lysophospholipid (20:5(5Z,8Z,11Z,14Z,17Z)/0:0), a phosphatidylcholine (P-18:1(9Z)/16:0) and also xi-8-hydroxyhexadecanedioic acid. Two metabolites negatively correlated with MDS, these were the monoacylglycerides (0:0/16:1(9Z)/0:0) and (0:0/20:3(5Z,8Z,11Z)/0:0). By stepwise elimination we selected a panel of 3 highly discriminatory metabolites and developed a linear regression model which identified 'high MDS' individuals with high sensitivity and specificity [AUC (95% CI) 0.83 (0.76–0.97)]. Conclusion: Our study highlights the utility of metabolomics as an approach for developing novel panels of dietary biomarkers. Quantitative profiling of these metabolites is required to validate their utility for evaluating dietary adherence. [ABSTRACT FROM AUTHOR]

Anopheles arabiensis and Anopheles funestus sensu stricto mosquitoes are major East African malaria vectors. Understanding their dispersal and population structure is critical for developing effective malaria control tools. Three mark-release-recapture (MRR) experiments were conducted for 51 nights to assess daily survival and flight range of An. arabiensis and An. funestus mosquitoes in south-eastern, Tanzania. Mosquitoes were marked with a fluorescent dye as they emerged from breeding sites via a self-marking device. Mosquitoes were collected indoors and outdoors using human landing catches (HLC) and Centers for Disease Control and Prevention light traps (CDC-LT). In total, 4210 An. arabiensis and An. funestus were collected with 316 (7.5%) marked and recaptured (MR). Daily mean MR was 6.8, standard deviation (SD ± 7.6) for An. arabiensis and 8.9 (SD ± 8.3) for An. funestus. Probability of daily survival was 0.76 for An. arabiensis and 0.86 for An. funestus translating into average life expectancy of 3.6 days for An. arabiensis and 6.5 days for An. funestus. Dispersal distance was 654 m for An. arabiensis and 510 m for An. funestus. An. funestus life expectancy was substantially longer than that of An. arabiensis. The MRR method described here could be routinely utilized when evaluating the impact of new vector control tools on mosquito survival. [ABSTRACT FROM AUTHOR]

To examine the (i) relationships between various body mass index (BMI)-derived metrics for measuring severe obesity (SO) over time based the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) references and (ii) ability of these metrics to discriminate children and adolescents based on the presence of cardiometabolic risk factors. In this cohort study completed from 2013 to 2021, we examined data from 3- to 18-year-olds enrolled in the CANadian Pediatric Weight management Registry. Anthropometric data were used to create nine BMI-derived metrics based on the CDC and WHO references. Cardiometabolic risk factors were examined, including dysglycemia, dyslipidemia, and elevated blood pressure. Analyses included Pearson correlations, intraclass correlation coefficients (ICC), and receiver operator characteristic area-under-the-curve (ROC AUC). Our sample included 1,288 participants (n = 666 [52%] girls; n = 874 [68%] white). The prevalence of SO varied from 60–67%, depending on the definition. Most BMI-derived metrics were positively and significantly related to one another (r = 0.45–1.00); ICCs revealed high tracking (0.90–0.94). ROC AUC analyses showed CDC and WHO metrics had a modest ability to discriminate the presence of cardiometabolic risk factors, which improved slightly with increasing numbers of risk factors. Overall, most BMI-derived metrics rated poorly in identifying presence of cardiometabolic risk factors. Conclusion: CDC BMI percent of the 95th percentile and WHO BMIz performed similarly as measures of SO, although neither showed particularly impressive discrimination. They appear to be interchangeable in clinical care and research in pediatrics, but there is a need for a universal standard. WHO BMIz may be useful for clinicians and researchers from countries that recommend using the WHO growth reference. What is Known: • Severe obesity in pediatrics is a global health issue. • Few reports have evaluated body mass index (BMI)-derived metrics based on the World Health Organization growth reference. What is New: • Our analyses showed that the Centers for Disease Control and Prevention BMI percent of the 95thpercentile and World Health Organization (WHO) BMI z-score (BMIz) performed similarly as measures of severe obesity in pediatrics. • WHO BMIz should be a useful metric to measure severe obesity for clinicians and researchers from countries that recommend using the WHO growth reference. [ABSTRACT FROM AUTHOR]

Malaria mosquitoes acoustically detect their mating partners within large swarms that form transiently at dusk. Indeed, male malaria mosquitoes preferably respond to female flight tones during swarm time. This phenomenon implies a sophisticated context- and time-dependent modulation of mosquito audition, the mechanisms of which are largely unknown. Using transcriptomics, we identify a complex network of candidate neuromodulators regulating mosquito hearing in the species Anopheles gambiae. Among them, octopamine stands out as an auditory modulator during swarm time. In-depth analysis of octopamine auditory function shows that it affects the mosquito ear on multiple levels: it modulates the tuning and stiffness of the flagellar sound receiver and controls the erection of antennal fibrillae. We show that two α- and β-adrenergic-like octopamine receptors drive octopamine's auditory roles and demonstrate that the octopaminergic auditory control system can be targeted by insecticides. Our findings highlight octopamine as key for mosquito hearing and mating partner detection and as a potential novel target for mosquito control. Malaria mosquitoes use their ears to detect the flight tones of mating partners in the swarm as part of the courtship ritual. Here, the authors describe the auditory role of octopamine as a modulator of auditory plasticity in malaria mosquitoes and identify the main receptors involved in this process. [ABSTRACT FROM AUTHOR]

Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as 'attract-and-kill' or 'push-and-pull', have been suggested as complementary tools to indoor residual spraying and long-lasting insecticidal nets. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions. A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a 'push' intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a 'pull' intervention placing an odour-baited mosquito trap at a 5 m distance from a house; the combined 'push–pull' package; and the control where houses contained all elements but without active ingredients. Treatments were rotated through 12 houses in a randomized-block design. Outdoor biting was estimated using human landing catches, and indoor mosquito densities using light-traps. None of the interventions provided any protection from outdoor biting malaria vectors. The 'push' reduced indoor vector densities dominated by Anopheles funestus by around two thirds. The 'pull' device did not add any benefit. In the light of the high Anopheles arabiensis biting densities outdoors in the study location, the search for efficient outdoor protection and effective pull components needs to continue. [ABSTRACT FROM AUTHOR]

The rate of strokes in Africa, particularly among lower socio-economic classes, is increasing. The impact on long-term, informal caregivers of stroke patients is not known, as most research has focused on acute and discharge care. This study reports on the findings from a study of in-depth qualitative interviews with 20 caregivers to family members with stroke diagnoses in Lomé, Togo. Findings show that social, structural, and relational forces greatly impact the lives of informal caregivers. This study offers an understanding of the caregivers' challenges through an intersectional framework which can be used to inform socio-economic, emotional, and health system supports for caregivers. [ABSTRACT FROM AUTHOR]

Language is an integral part of marketing. Consumers share word of mouth, salespeople pitch services, and advertisements try to persuade. Further, small differences in wording can have a big impact. But while it is clear that language is both frequent and important, how can we extract insight from this new form of data? This paper provides an introduction to the main approaches to automated textual analysis and how researchers can use them to extract marketing insight. We provide a brief summary of dictionaries, topic modeling, and embeddings, some examples of how each approach can be used, and some advantages and limitations inherent to each method. Further, we outline how these approaches can be used both in empirical analysis of field data as well as experiments. Finally, an appendix provides links to relevant tools and readings to help interested readers learn more. By introducing more researchers to these valuable and accessible tools, we hope to encourage their adoption in a wide variety of areas of research. [ABSTRACT FROM AUTHOR]

Developing CAR T cells for acute myeloid leukemia (AML) has been hampered by a paucity of targets that are expressed on AML blasts and not on hematopoietic progenitor cells (HPCs). Here we demonstrate that GRP78 is expressed on the cell surface of primary AML blasts but not HPCs. To target GRP78, we generate T cell expressing a GRP78-specific peptide-based CAR, which show evidence of minimal fratricide post activation/transduction and antigen-dependent T cell differentiation. GRP78-CAR T cells recognize and kill GRP78-positive AML cells without toxicity to HPCs. In vivo, GRP78-CAR T cells have significant anti-AML activity. To prevent antigen-dependent T cell differentiation, we block CAR signaling and GRP78 cell surface expression post activation by using dasatinib during GRP78-CAR T cell manufacturing. This significantly improves their effector function in vitro and in vivo. Thus, targeting cell surface GRP78-positive AML with CAR T cells is feasible, and warrants further active exploration. There is an unmet need to discover suitable targets for CAR-T therapy in patients with acute myeloid leukemia (AML). Here the authors show that GRP78, a key regulator of the unfolded protein response, is highly expressed on the surface of primary AML blasts, but not on normal lymphocytes and hematopoietic progenitor cells, and that GRP78-CAR T have anti-AML activity in preclinical models. [ABSTRACT FROM AUTHOR]

Background: Expediting cancer diagnosis may be achieved by targeted decreases in referral thresholds to increase numbers of patients referred for urgent investigation.Methods: Clinical Practice Research Datalink data from England for 150,921 adults aged ≥40 were used to identify participants with features of possible cancer equating to risk thresholds ≥1%, ≥2% or ≥3% for breast, lung, colorectal, oesophago-gastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial and laryngeal cancers.Results: The mean age of participants was 60 (SD 13) years, with 73,643 males (49%). In 2016, 8576 consultation records contained coded features having a positive predictive value (PPV) of ≥3% for any of the 11 cancers. This equates to a rate of 5682/100,000 patients compared with 4601/100,000 Suspected Cancer NHS referrals for these cancers from April 2016-March 2017. Nine thousands two hundred ninety-one patient-consultation records had coded features equating to a ≥2% PPV, 8% more than met PPV ≥ 3%. Similarly, 19,517 had features with a PPV ≥ 1%, 136% higher than for PPV ≥ 3%.Conclusions: This study estimated the number of primary-care patients presenting at lower thresholds of cancer risk. The resource implications of liberalising this threshold to 2% are modest and manageable. The details across individual cancer sites should assist planning of English cancer services. [ABSTRACT FROM AUTHOR]

This study explored mediating pathways, moderating factors, and moderated mediation effects of a web-based, cognitive behavioral therapy (CBT) intervention for chronic pain patients with aberrant drug-related behavior (ADRB). In a 2-arm RCT, patients with chronic pain who screened positive for ADRB received treatment-as-usual (TAU, n = 55) or TAU plus a 12-week, web-based CBT intervention (n = 55). Assessments were conducted at weeks 4, 8, and 12, and at 1- and 3-months post intervention. Web-CBT significantly reduced pain catastrophizing, which, in turn, reduced pain interference and pain severity via a pathway of pain catastrophizing. Web-CBT also significantly reduced ADRB both directly and indirectly by reducing pain catastrophizing. For pain interference and pain severity, web-CBT was more effective than TAU for younger patients (≤ age 50). For pain severity, web-CBT was more effective for both younger patients (≤ age 50), and those with a lifetime substance use disorder. Findings suggest that web-CBT's positive impact on pain outcomes and ADRB are mediated by its effect on pain catastrophizing, and its treatment effects may be most robust for younger patients and those with histories of substance dependence. [ABSTRACT FROM AUTHOR]

Both endovascular repair (EVR) and open repair (OR) surgery of thoraco-abdominal aortic aneurysms cause spinal cord (SC) injury that can lead to paraparesis or paraplegia. It has been assumed that mechanisms responsible for SC damage after EVR are similar to those after OR. This pilot study compared the pathophysiology of SC injury after EVR versus OR using a newly developed EVR dog model. An increasing number of stents similar to those used in patients were inserted in the aorta of three dogs to ensure thoracic or thoracic plus lumbar coverage. The aorta of OR dogs was cross-clamped for 45 min. Behavior assessment demonstrated unique patterns of proprioceptive ataxia and evolving paraparesis in EVR versus irreversible paraplegia in OR. MRI showed posterior signal in lumbar SC after EVR versus central cord edema after OR. Histopathology showed white matter edema in L3–L5 localized to the dorsal column medial lemniscus area associated with loss of myelin basic protein but not neurons after EVR, versus massive neuronal loss in the gray matter in L3–L5 after OR. Metabolome analysis demonstrates a distinctive chemical fingerprint of cellular processes in both interventions. Our results call for the development of new therapeutics tailored to these distinct pathophysiologic findings. [ABSTRACT FROM AUTHOR]

Asymmetry of striatal dopaminergic deficits and motor symptoms is a typical characteristic of idiopathic Parkinson's disease (PD). This study aims to characterise the trend of asymmetry in moderate-stage PD. We performed a 19-month longitudinal study in 27 patients with PET-CT imaging and appropriate clinical assessments. 11C-PE2I non-displaceable binding potential (BPND) was calculated bilaterally for the striatum at baseline and follow-up to estimate the in vivo density of striatal dopamine transporters (DAT). Changes in striatal 11C-PE2I BPND over time were more prominent in the ipsilateral as compared to contralateral side. Changes in MDS-UPDRS-III (motor component of the Movement Disorders Society Unified PD Rating Scale) were not different between the clinically most and least affected body sides. Our data support that the asymmetry in striatal dopaminergic degeneration becomes less prominent in moderate-stage PD. In contrast, during the above period, the asymmetry of motor symptoms was maintained between the clinically most and least affected body sides. [ABSTRACT FROM AUTHOR]

Background: Substance use frequently goes undetected in primary care. Though barriers to implementing systematic screening for alcohol and drug use have been examined in urban settings, less is known about screening in rural primary care.Objective: To identify current screening practices, barriers, facilitators, and recommendations for the implementation of substance use screening in rural federally qualified health centers (FQHCs).Design: As part of a multi-phase study implementing electronic health record-integrated screening, focus groups (n = 60: all stakeholder groups) and individual interviews (n = 10 primary care providers (PCPs)) were conducted.Participants: Three stakeholder groups (PCPs, medical assistants (MAs), and patients) at three rural FQHCs in Maine.Approach: Focus groups and interviews were recorded, transcribed, and content analyzed. Themes surrounding current substance use screening practices, barriers to screening, and recommendations for implementation were identified and organized by the Knowledge to Action (KTA) Framework.Key Results: Identifying the problem: Stakeholders unanimously agreed that screening is important, and that universal screening is preferred to targeted approaches. Adapting to the local context: PCPs and MAs agreed that screening should be done annually. Views were mixed regarding the delivery of screening; patients preferred self-administered, tablet-based screening, while MAs and PCPs were divided between self-administered and face-to-face approaches. Assessing barriers: For patients, barriers to screening centered around a perceived lack of rapport with providers, which contributed to concerns about trust, judgment, and privacy. For PCPs and MAs, barriers included lack of comfort, training, and preparedness to address screening results and offer treatment.Conclusions: Though stakeholders agree on the importance of implementing universal screening, concerns about the patient-provider relationship, the consequences of disclosure, and privacy appear heightened by the rural context. Findings highlight that strong relationships with providers are critical for patients, while in-clinic resources and training are needed to increase provider comfort and preparedness to address substance use. [ABSTRACT FROM AUTHOR]

In the post-violation model of the psychological contract, employees who have experienced violation engage in a variety of coping strategies and, more often than not, form a new psychological contract and continue to work for their employer. Our study applies this theoretical model to actual employees’ descriptions of how they deal with psychological contract violation and develop new psychological contracts. We collected interview data from 27 employees at a large manufacturing organization in which dramatic, irreversible company-wide change not only violated employees’ psychological contracts but also provided few obvious opportunities to repair them. Through template analysis of interview transcripts, we chronicle employees’ coping processes, inventory their new psychological contracts, and assess the quality of their employment relationships. We found that some employees effected extensive changes to their psychological contracts, some engaged in an unexpectedly long process of adjustment, and some compromised their self-interest to uphold their pre-violation psychological contracts. Our findings generally map to the post-violation model, but with important refinements that accentuate employees’ role in recreating their psychological contracts, the durability of their psychological contracts, and the role of the psychological contract as a coping mechanism. [ABSTRACT FROM AUTHOR]

Previous research on employee psychological contracts has focused on three different types of expectations that workers have of their employers: transactional exchange of economic currency, relational exchange of socioemotional currency, and, more recently, covenantal exchange of ideological currency. This last type of currency, however, has been studied almost entirely in nonprofit workplaces among employees in helping professions (e.g., healthcare, education) who hold advanced degrees. Although not explicit in the extant literature, the implication of such is that expressions of ideological currency may be limited to certain types of professions. In the present study, we therefore analyzed both white and blue-collar employees' ideological expectations in a corporate, for-profit, manufacturing environment. Using 1492 responses to an open-ended question received from an email survey, we found that 36% contained an expression of ideological currency, with an additional 44.8% possessing a possible expression of ideological currency. Comparisons of these expressions reveal many similarities between white and blue-collar employees within this organization as well as between these employees and those found in the published literature from workers in other industries. We discuss the implications of these findings for theory and future research. [ABSTRACT FROM AUTHOR]

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. B Correction to: Marketing Letters b https://doi.org/10.1007/s11002-022-09635-6 In this article the title was incorrectly given as "Wisdom from words: marketing insights from text" but should have been "Marketing insights from text analysis". [Extracted from the article]

Arsenic (As) is a ubiquitous metalloid known for its adverse effects to human health. Microorganisms are also impacted by As toxicity, including methanogenic archaea, which can affect the performance of a process in which biological activity is required (i.e., stabilization of activated sludge in wastewater treatment plants). The novel ability of a mixed methanogenic granular sludge consortium to adapt to the inhibitory effect of arsenic As was investigated by exposing the culture to approximately 0.92 mM of arsenite (As) for 160 days in an arsenate (As)-reducing bioreactor using ethanol as the electron donor. The results of shaken batch bioassays indicated that the original, unexposed sludge was severely inhibited by As as evidenced by the low 50 % inhibition concentrations (IC) determined, i.e., 19 and 90 μM As for acetoclastic and hydrogenotrophic methanogenesis, respectively. The tolerance of the acetoclastic and hydrogenotrophic methanogens in the sludge to As increased 47-fold (IC = 910 μM) and 12-fold (IC = 1100 μM), respectively, upon long-term exposure to As. In conclusion, the methanogenic community in the granular sludge demonstrated a considerable ability to adapt to the severe inhibitory effects of As after a prolonged exposure period. [ABSTRACT FROM AUTHOR]

The study investigated if establishing common international security standards through mutually recognized security programs would make the air cargo supply chain less vulnerable to terrorist activity and increase trade efficiencies. Divergent air cargo security programs result in separate measures that lack a unified front against terrorism and slow the shipping process. By proposing the Global Protocol for Air Cargo (GPAC) to the aviation security community, I examine the idea of an international framework to unite government and industry to create the most secure and efficient aviation cargo supply chain to date. The research overall explores ways to unify air cargo stakeholders by raising the bar on security measures and absorbing the burdens placed on securing the aviation industry. [ABSTRACT FROM AUTHOR]

Much of the extant literature regarding generational cohort differences has been conducted on college-educated participants, a potential bias noted by previous researchers. The present study therefore examines generational cohort differences in workplace expectations between professional (i.e., 'white-collar,' largely college educated) and production (i.e., 'blue-collar,' largely non-college educated) workers. Using online survey data from 2,799 union workers employed by the same organization, we compared expectations when first hired as well as current workplace expectations between professional and production workers from three different generational cohorts (i.e., Gen Y, Gen X, and Baby Boomer). We found evidence for generational differences that confirms some of the common characterizations of Gen Y workers; however, this characterization was principally found within our professional subgroup of Gen Y employees. Further, the data suggest that other factors (e.g., workplace experiences, maturation effects) may shape current workplace expectations more than do generational differences. These results suggest that concern over generational differences may be limited to certain workplace expectations and to specific subgroups of employees. [ABSTRACT FROM AUTHOR]

Old paradigms in environmental studies are being challenged and giving way to new ones. Discussions of scarcity, wilderness, and restoration have all evolved in the context of the Anthropocene. Learning the vocabulary of environmental studies in a world of conceptual diversity and ongoing change is an enormous challenge for students. Students themselves have changed in recent years as well, with traditional environmental learners being joined by a diversity of those interested in commerce or justice. These kinds of upheavals present challenges for teaching and learning in environmental studies. This is in part because the growing diversity of perspectives is difficult to metabolize in traditional approaches to teaching, many older concepts still enjoy popular hegemony, and debates over these questions are often rarified, abstract, and difficult to ground. We therefore propose an approach that mobilizes teaching through objects, where common and material things-bottled water, wolves, e-waste, trees, or lawns-are used as case objects from which learning begins. We maintain that such an approach, though not new, allows environmental studies to move beyond environmental problems. We further suggest that this approach better allows students to compare, address, exercise, and critique diverse theoretical ways of thinking about human-environment relationships. Finally, we believe that this approach is potentially transformational for learning in the field, simply because upending banal and familiar material things through iterative inquiry has the most immediate and affective potential for truly reaching students and transforming the way they think about the environment. [ABSTRACT FROM AUTHOR]

A novel protein scaffold based on the cystine knot domain of the agouti-related protein (AgRP) has been used to engineer mutants that can bind to the αβ integrin receptor with high affinity and specificity. In the current study, an F-labeled AgRP mutant (7C) was prepared and evaluated as a positron emission tomography (PET) probe for imaging tumor angiogenesis. AgRP-7C was synthesized by solid phase peptide synthesis and site-specifically conjugated with 4-nitrophenyl 2-F-fluoropropionate (F-NFP) to produce the fluorinated peptide, F-FP-AgRP-7C. Competition binding assays were used to measure the relative affinities of AgRP-7C and F-FP-AgRP-7C to human glioblastoma U87MG cells that overexpress αβ integrin. In addition, biodistribution, metabolic stability, and small animal PET imaging studies were conducted with F-FP-AgRP-7C using U87MG tumor-bearing mice. Both AgRP-7C and F-FP-AgRP-7C specifically competed with I-echistatin for binding to U87MG cells with half maximal inhibitory concentration (IC) values of 9.40 and 8.37 nM, respectively. Non-invasive small animal PET imaging revealed that F-FP-AgRP-7C exhibited rapid and good tumor uptake (3.24 percentage injected dose per gram [% ID/g] at 0.5 h post injection [p.i.]). The probe was rapidly cleared from the blood and from most organs, resulting in excellent tumor-to-normal tissue contrasts. Tumor uptake and rapid clearance were further confirmed with biodistribution studies. Furthermore, co-injection of F-FP-AgRP-7C with a large molar excess of blocking peptide c(RGDyK) significantly inhibited tumor uptake in U87MG xenograft models, demonstrating the integrin-targeting specificity of the probe. Metabolite assays showed that the probe had high stability, making it suitable for in vivo applications. F-FP-AgRP-7C exhibits promising in vivo properties such as rapid tumor targeting, good tumor uptake, and excellent tumor-to-normal tissue ratios, and warrants further investigation as a novel PET probe for imaging tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Bioreactance is a novel non-invasive method for cardiac output measurement that involves the analysis of blood flow-dependent changes in the phase shifts of electrical currents applied across the chest. The present study (1) compared resting and exercise cardiac outputs determined by bioreactance and bioimpedance methods and those estimated from measured oxygen consumption, (2) determined the relationship between cardiac output and oxygen consumption, and (3) assessed the agreement between the bioreactance and bioimpedance methods. Twelve healthy subjects (aged 30 ± 4 years) performed graded cardiopulmonary exercise test on a recumbent cycle ergometer on two occasions, 1 week apart. Cardiac output was monitored at rest, at 30, 50, 70, 90, 150 W and at peak exercise intensity by bioreactance and bioimpedance and expired gases collected. Resting cardiac output was not significantly different between the bioreactance and bioimpedance methods (6.2 ± 1.4 vs. 6.5 ± 1.4 l min, P = 0.42). During exercise cardiac outputs were correlated with oxygen uptake for both bioreactance (r = 0.84, P < 0.01) and bioimpedance techniques (r = 0.82, P < 0.01). At peak exercise bioimpedance estimated significantly lower cardiac outputs than both bioreactance and theoretically calculated cardiac output (14.3 ± 2.6 vs. 17.5 ± 5.2 vs. 16.9 ± 4.9 l min, P < 0.05). Bland-Altman analyses including data from rest and exercise demonstrated that the bioimpedance method reported ~1.5 l min lower cardiac output than bioreactance with lower and upper limits of agreement of −2.98 to 5.98 l min. Bioimpedance and bioreactance methods provide different cardiac output estimates, particularly at high exercise intensity, and therefore the two methods cannot be used interchangeably. In contrast with bioimpedance, bioreactance cardiac outputs are similar to those estimated from measured oxygen consumption. [ABSTRACT FROM AUTHOR]

The current study examined how work support resources and working from home influenced forms of work-family conflict (WFC) in employees at a large corporation. Scales measuring employee’s general WFC, time-based WFC, and strain-based WFC were used to evaluate the extent to which employees experienced work-induced conflict at home. Two forms of working at home were assessed, days worked at home and extra hours worked at home, and five variables measured the extent of one’s support resources: work social support, organizational support, individual consideration from one’s manager, idealized influence from one’s manager and contingent reward from one’s manager. We predicted that days worked at home would be negatively related to the three forms of WFC, while the extra hours worked at home would be positively related. Moreover, we hypothesized that the five support variables would moderate the relationship between extra hours worked at home and the types of WFC. The data supported some of the predictions, and the implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Scrapie belongs to a group of diseases known as the transmissible spongiform encephalopathies or prion diseases. Two different categories of naturally occurring scrapie have been identified: classical scrapie, which was first recorded around 1750, and atypical scrapie or ‘Nor-98’, which was first identified in Norway in 1998. The molecular characteristics of atypical scrapie have been well defined, but detailed descriptions of the neuropathological phenotype are rare since the majority of cases have been detected through active surveillance programmes where only brainstem and cerebellum are collected for statutory diagnosis. In order to characterise the neuropathology of naturally occurring atypical scrapie in sheep, we examined multiple brain levels from 15 whole brains from field cases of atypical scrapie, both clinical suspects and fallen stock, collected in Great Britain between 2004 and 2006. We found that the distribution of disease-associated prion protein (PrPSc) and vacuolation in atypical scrapie cases are very different to both classical scrapie and experimental bovine spongiform encephalopathy in sheep. Immunolabelling for PrPSc is mild and restricted at the obex and more intense and widespread rostrally, particularly in the cerebellum, substantia nigra, thalamus and basal nuclei. Intracellular immunolabelling types are not seen, but distinctive white matter immunolabelling is widespread. Vacuolation associated with PrPSc deposits was not observed in the brainstem neuroanatomical areas commonly affected in classical scrapie and bovine spongiform encephalopathy, but was instead most prominent in the cerebellar cortex and neocortex. This is the largest comprehensive descriptive study of atypical scrapie pathology to date, and provides baseline data against which other natural or experimental cases can be compared. It also reinforces the current recommendation to collect cerebellum in addition to brainstem to enable confident confirmation of this distinct disease phenotype within surveillance programmes. [ABSTRACT FROM AUTHOR]

In the present study, we explore agreement between company versus self-reported reasons for job loss and the degree of perceived control employees report over the job loss, looking to see if either job loss type or perceived control is related to subsequent levels of mastery and depression. Two thousand two hundred seventy-nine of 3,700 (61%) employees responded to a survey at Time One; of these participants, 310 later lost their jobs and were mailed a Time Two survey. Comparison of self- versus company-reported reasons for the job loss from the 171 usable surveys (55% response rate) revealed relatively good agreement. Roughly one third of the former employees, however, categorized the job loss in more than one way. There was also a very strong tendency for employees to report that they had very high control over the decision to leave the company, and nearly all employees reported improvements to their levels of mastery and depression; exceptions to this pattern were observed for those losing their jobs due to “rule violation” or “involuntary layoff.” Control over the job loss was related to Time Two levels of mastery and depression, but only weakly related to changes in these outcomes moving from Time One to Time Two. [ABSTRACT FROM AUTHOR]

The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P=0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P<0.0001 and P=0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P=0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design. [ABSTRACT FROM AUTHOR]

This paper presents preliminary evidence on the internal consistency and validity of a scale designed to measure the degree to which one believes women managers experience a greater number of obstacles and more critical judgments about their work performance as compared to managerial men (the Stereotype Beliefs about Women Managers scale; SBWMS). Survey data from 1,337 managerial and non-managerial men and women employed by a large manufacturing organization revealed that the 6-item scale possessed a single factor. Significant mean group differences and correlations between the SBWMS and a number of organizationally-relevant measures provide good preliminary support for the scale's validity. [ABSTRACT FROM AUTHOR]

COGNITIVE STYLE is a “potent learner characteristic that can have a significant effect on learner achievement” (Hayes & Allinson, 1997, p. 185). However, further exploration is required before links among cognitive style, performance, and other aspects of learners’ experience are more clearly understood. This study explores the relationship among cognitive style, performance, gender, and communication in a particular educational setting. The sample consisted of 145 new computer-systems students at the beginning of a program of study in their first year of higher education. Participants completed the “Cognitive Style Index” (Allinson & Hayes, 1996) and provided additional demographic data, including gender and recent academic performance. Qualitative information about learning expectations was also sought. Findings show a significant relationship between performance and cognitive style. Students whose cognitive style scores indicate a preference for analytical thinking are significantly more likely to have entered university with above average performance scores than those with a preference for intuition. A significant relationship was also identified between cognitive style and types of qualitative statements used to describe learning expectations. The educational implications of these findings are explored and discussed. [ABSTRACT FROM AUTHOR]

Sanford and Fawcett (1980) developed an approach for increasing informed public opinion called consequence analysis, in which more thoughtful, better informed opinions appeared to result from a procedure in which respondents were asked to consider, elaborate, and evaluate the multiple consequences of a public policy decision. In this partial replication, 43 persons responded to an internet-based instrument that tested the effects of an online consequence analysis procedure. The results indicated that the procedure produced significant changes in stated opinions in the direction of opinions more consistent with the science of behavior, supporting the initial findings of Sanford and Fawcett, but also that many respondents did not complete the on-line instrument. Implications for further research, and the possible substantial importance of the consequence analysis procedure for expanding "self-reflective society" are explored. [ABSTRACT FROM AUTHOR]

In the present study, we examined alcohol consumption and alcohol problems between managerial and nonmanagerial men and women. We also examined alcohol problems as a function of drinking context (i.e., when they drink and with whom they drink) for each of these four groups. Survey data and data from company records were collected from a large sample of blue and white collar employees (n = 2279). Participants completed a detailed questionnaire aimed at assessing many work-related attitudes, general mental and physical health-related perceptions, motivations for alcohol use, alcohol consumption indices, and alcohol problems. We found that several of the demographic variables differentially predicted alcohol consumption and problems for the four groups. In addition, drinking alone and immediately after work were associated with alcohol problems for women managers at a significantly higher rate than for the other groups of employees. These results support the assertion that more complex models are needed to understand the linkages between work and alcohol use. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance to chemotherapeutic agents as a result of β1 integrin-stimulated tyrosine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking β1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC. [ABSTRACT FROM AUTHOR]

The article focuses on the correlation between drug testing policies of the companies and job attitudes of the employees. In an attempt to curb work related alcohol and drug use, many employers currently use drug testing (DT) as a means of both screening job applicants and monitoring job incumbents. The characteristics of these programs vary widely: reasons for testing range from random, mandatory screens to "for cause" testing, while test outcomes range from substance abuse treatment to immediate dismissal. The purpose of the present investigation is to examine DT attitudes with respect to a number of work-related attitudes and behaviors using a large, blue collar sample. Apparent danger on the job and public contact are two variables that have been significantly related to DT attitudes. Attitudes toward DT programs have been examined with respect to both procedural and outcome aspects of the DT program. Limited evidence suggests that drug testing programs arc received more favorably when employees perceive them to be fair and when the program is designed to protect worker privacy.

Induction of unrepairable DNA damage, accumulation of misrepaired DNA damage, and generation of imbalances in competing biochemical and/or metabolic processes have been proposed to explain the relationship between radiation-induced DNA damage and cell lethality. Theoretically, the temperature dependence of the critical DNA repair process(es) should be 1) either independent of or identical to the temperature dependence of cell killing if the first two hypotheses are correct, and 2) different if the third hypothesis is correct. To test this, exponentially growing rat 9L brain tumor cells were left at 37°C or equilibrated for 3-14 h at 20°C before irradiation. Cells were irradiated and allowed to repair at either 20°C or 37°C. Alternatively, the cells were irradiated at one of these temperatures and immediately shifted to the other temperature for repair. DNA damage was assessed by the alkaline elution technique; cell kill was assessed by a clonogenic assay. 9L cells maintained at 20°C or 37°C sustained the same amount of DNA damage as measured by alkaline elution. DNA repair instantaneously assumed the rate characteristic of the postirradiation temperature. For 9L cells equilibrated, irradiated, and repaired at 20°C, the half-time of the fast phase of the DNA repair decreased by a factor of ≈2 and the half-time of the slow phase decreased by a factor of ≈5 over that measured in cells incubated, irradiated and repaired at 37°C. Although the rate of DNA repair decreased substantially at 20°C, the survival of 9L cells that were equilibrated and irradiated at 20°C was greater ( p <10) than those incubated and irradiated at 37°C, when assayed by an immediate plating protocol. In addition, the survival of 9L cells equilibrated and irradiated at 20°C and then shifted to 37°C immediately after irradiation was greater ( p <10) than that obtained with any other delayed plating protocol. Thus, the temperature dependence of the DNA repair processes measured by alkaline elution was different from the temperature dependence of cell killing measured either by an immediate or delayed plating protocol. These data support the hypothesis that many irradiated 9L tumor cells die because of imbalances in sets of competing biochemical and/or metabolic processes. [ABSTRACT FROM AUTHOR]