Online Search Strategies and Results From a Crowdsourced Survey on Asymptomatic Bacteriuria.

IMPORTANCE: Despite the prevalence of asymptomatic bacteriuria (ASB), what proportion of the population is aware of this condition and the quality of internet resources are currently unknown. OBJECTIVE: This study aimed to use an online crowdsourcing platform to explore general knowledge and internet search strategies, along with the quality of information, on ASB. STUDY DESIGN: An online survey was administered through a crowdsourcing platform to women 50 years or older via Qualtrics, which is a sophisticated online survey tool. Participants completed a survey on ASB, and participants were asked how they would search the internet for information both on urinary test results and on ASB. Outcomes included survey responses, and qualitative data were coded and analyzed thematically. χ2 Testing and regression modeling were used to look for variables associated with concern for ASB. RESULTS: There were a total of 518 participants who passed attention check qualifications, and only 45 respondents (8.7%) had heard of ASB. Many were concerned about progress to a worsening infection (n = 387 [77.6%]). When controlling for confounders, education beyond a college degree was not associated with a lower concern for ASB when compared with those with a high school education or less (adjusted odds ratio, 0.63; 95% confidence interval, 0.25-1.55; P = 0.31). Medical providers were the target audience for a majority of the websites, and many of the patient-facing results were of poor quality. CONCLUSIONS: Our national survey of women demonstrated a prevalent knowledge deficit surrounding ASB. We must seek to create high-quality, readily available, patient-facing information to increase awareness of ASB, allay concerns, and increase antibiotic stewardship.

Sex, Gender, and Sexual Orientation in Psychological Research: Exploring Data Trends & Researcher Opinions.

Psychology researchers have historically neglected variables related to sex, gender, and sexual orientation, leading to the erasure of sex, gender, and sexual orientation in research, which limits the generalizability of psychological findings. We argue that these important variables need to be considered more consistently by researchers across psychology subdisciplines. In Study 1 we found that 15.1% of a large MTurk sample (i.e., 8500+) identified as a sexual or gender minority (SGM; e.g., lesbian, gay, bisexual, transgender, queer [LGBTQ+]). In addition, data from Study 1 showed that our youngest cohort (i.e., aged 18-25 years) reported significantly higher rates of LGBTQ+ identification (22.7%) than our oldest cohort (i.e., 65-84 years; 1.3%), suggesting that endorsement of these idnetities is increasing. Next, in Study 2 we found that psychology researchers (N = 135) tended to rate expansive sex, gender, and sexual orientation demographic variables as important in general, but were much less likely to report actually using these variables in their own studies. Moreover, younger faculty and faculty who identified as women rated these variables as more important than their colleagues. Based on our findings, we conclude that psychology researchers should use expansive sex, gender, and sexual orientation items in their studies, report these demographic variables consistently, and analyze their data by these important variables when possible. Because a substantial and growing proportion of individuals identify as LGBTQ+, and because SGM identity is related to additional life stressors, it is imperative to better understand these individuals. Various resources are offered and challenges are discussed.

Systematic Review and Meta-Analyses: Safety and Efficacy of Complementary and Alternative Treatments for Pediatric Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Complementary and alternative treatments (CATs) for ADHD have proliferated over the past decade; however, their safety and efficacy remain uncertain. We completed a systematic review and meta-analyses across CAT domains. METHODS: Systematic search and data extraction identified randomized controlled trials for pediatric ADHD (ages 3-19 years) that included probably blind ADHD symptom outcome measures. We evaluated basic (RCT of a CAT compared with sham/placebo, attention/active control, treatment as usual, and waitlist control), complementary (RCTs comparing an evidence-based treatment with a CAT and the same evidence-based treatment), and alternative (evidence-based treatment to CAT) efficacy. Random-effect meta-analyses were conducted when at least 3 blinded studies were identified for a specific CAT domain. RESULTS: Eighty-seven of 2253 nonduplicate screened manuscripts met inclusion criteria. No study reported significantly greater adverse effects for CATs than controls; naturopathy reported fewer adverse effects than evidence-based treatments but did not demonstrate basic efficacy. In the systematic review of basic efficacy, evidence of effectiveness was mixed but replicated previous evidence for the possible efficacy of cognitive training, neurofeedback, and essential fatty acid supplementation for certain patients. With respect to alternative and complementary efficacy, no CAT outperformed or enhanced evidence-based treatments (stimulant medications and behavioral therapy) when replication was required. Individual meta-analyses indicated that cognitive training was the only CAT that demonstrated overall basic efficacy ( SMD = 0.216; p = 0.032). CONCLUSION: Clinicians may cautiously recommend (but monitor) cognitive training when evidence-based treatments are not feasible or effective for a patient. Additional studies are needed to further understand the potential of CAT domains.

Are There Long-Term Effects of Behavior Therapy for Adolescent ADHD? A Qualitative Study.

We utilized qualitative methodology to characterize potential long-term effects (therapeutic and iatrogenic) of behavior therapy for adolescents with ADHD. Forty-two in-depth interviews were conducted with adolescents with ADHD and parents, 4 years post-treatment. Grounded theory methods identified and reported prevalence of themes. All reported long-term effects were classified as benefits; no iatrogenic effects were noted. Long-term impact themes reported for a majority of participants included: development of organization skills (81.0%), enhanced motivation (57.1%), improved self-awareness (57.1%), improved parental knowledge of ADHD (76.2%), increased parent autonomy granting (61.9%), enhanced parental engagement with the youth (52.4%), and improved parent-teen relationships (52.4%). Fourteen themes were present for smaller subsamples, including reduced need for medication (3 of 9 medicated participants). Experimental studies of behavior therapy for adolescent ADHD should measure themes detected herein and directly test the possibility of long-term treatment effects.

Feasibility and Acceptability of an Internet-Based Intervention for Young Adults with ADHD.

Internet-based interventions (IBIs) to treat psychological disorders are available, but accessibility to these to treat attention-deficit/hyperactivity disorder (ADHD) in young adult populations is quite limited. The current study examined the feasibility of a proposed IBI for ADHD and participant perceptions regarding treatment acceptability and credibility, and outcome expectancy. Participants (N = 235; aged 18-35) with a prior ADHD diagnosis were recruited through Amazon's Mechanical Turk (MTurk) and were provided with a proposed IBI and explanatory outlines of treatment module content. Participants in the cross-sectional study were randomly assigned to either a tailored (i.e., targeted content modules), minimal (i.e., presented overall fewer and non-targeted modules), or full (i.e., all possible modules) condition. Results demonstrated moderate IBI acceptability among participants in the tailored and full conditions. The majority of participants preferred IBI over face-to-face (F2F) treatment, and most individuals who preferred F2F treatment also considered an IBI to be an acceptable treatment modality. Lack of significant mean differences between the tailored and full conditions on several of the main outcomes of interest (e.g., perceptions of acceptability) suggests that implementation of either method of treatment could prove effective. Differences based on treatment length and relevance, and biological sex were also explored. Implications, limitations, and future directions are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s41347-022-00256-4.

Networks of ADHD and SCT Symptoms in Emerging Adulthood.

OBJECTIVE: Emerging adulthood (18-25 years) is a transitional and understudied developmental period. Yet, little is known about how specific symptoms of ADHD, as well as those from the related SCT domain, may differentially relate to one another during this period, if there are differences based on biological sex, or how closely results will align with adulthood. METHODS: We used network analysis techniques to explore the structure of ADHD and SCT symptoms within emerging adulthood, with additional comparisons between sexes as well as between emerging adulthood and adulthood. Using an online platform, 8,506 adults reported on their symptoms of ADHD and SCT. RESULTS: Symptoms grouped together within their respective domains during emerging adulthood with no significant differences in overall network structure between sexes. Similarly, network structure appeared to be robust across emerging adulthood and adulthood. CONCLUSION: Such consistency supports a conceptualization of ADHD in emerging adulthood as similar to adulthood.

Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo.

B-cell maturation antigen (BCMA) is an attractive therapeutic target highly expressed on differentiated plasma cells in multiple myeloma and other B-cell malignancies. GSK2857916 (belantamab mafodotin, BLENREP) is a BCMA-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory multiple myeloma. We report that GSK2857916 induces immunogenic cell death in BCMA-expressing cancer cells and promotes dendritic cell activation in vitro and in vivo GSK2857916 treatment enhances intratumor immune cell infiltration and activation, delays tumor growth, and promotes durable complete regressions in immune-competent mice bearing EL4 lymphoma tumors expressing human BCMA (EL4-hBCMA). Responding mice are immune to rechallenge with EL4 parental and EL4-hBCMA cells, suggesting engagement of an adaptive immune response, immunologic memory, and tumor antigen spreading, which are abrogated upon depletion of endogenous CD8+ T cells. Combinations with OX40/OX86, an immune agonist antibody, significantly enhance antitumor activity and increase durable complete responses, providing a strong rationale for clinical evaluation of GSK2857916 combinations with immunotherapies targeting adaptive immune responses, including T-cell-directed checkpoint modulators.

ADHD and SCT Symptomatology in Relation to College Students' Use of Self-Regulated Learning Strategies.

Objective: The present study examined the relation between self-regulated learning (SRL) strategies and ADHD and sluggish cognitive tempo (SCT) symptomatology. Method: Participants were 303 college students, aged 18 to 25 (M = 20.04, SD = 1.45), from a Midwestern university who completed the Barkley Adult ADHD Rating Scale-IV (BAARS-IV), and a shortened, generalized version of the Motivated Strategies for Learning Questionnaire (MSLQ). Results: Among college students, inattention symptomatology was consistently predictive of deficits in use of value, expectancy, and self-regulation strategies, while SCT symptomatology was only predictive of deficits in the use of self-regulation strategies. Conclusion: This study is the first to examine the relation between SCT symptomatology and SRL strategy use in college students. The findings revealed that SRL strategy use differs between college students exhibiting ADHD or SCT symptomatology. Remediation focusing on these deficits would likely increase academic achievement. Clinical implications, limitations, and suggestions for future research are discussed.

DSM-5 and Other Symptom Thresholds for ADHD: Which Is the Best Predictor of Impairment in College Students?

OBJECTIVE: Approximately 5% of adults have ADHD. Despite recommendations regarding the diagnosis of emerging adults, there is not a strong consensus regarding the ideal method for diagnosing ADHD in both emerging and mature adults. We were interested in determining whether a threshold of four, five, or six ADHD symptoms would be associated with significantly different levels of functional impairment and be more or less indicative of a potential ADHD diagnosis. METHOD: We examined the relation between functional impairment and these ADHD symptom thresholds in 2,577 college students. RESULTS: Our findings suggest that none of these symptom thresholds are differentially better at predicting functional impairment. CONCLUSION: The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) threshold of five symptoms for ages 17 years and older is not necessarily predictive of ADHD-related impairment in college students and may not be preferable to other thresholds. Options for resolving this diagnostic dilemma are discussed.

Thermal Boundary Conductance Across Heteroepitaxial ZnO/GaN Interfaces: Assessment of the Phonon Gas Model.

We present experimental measurements of the thermal boundary conductance (TBC) from 78-500 K across isolated heteroepitaxially grown ZnO films on GaN substrates. This data provides an assessment of the underlying assumptions driving phonon gas-based models, such as the diffuse mismatch model (DMM), and atomistic Green's function (AGF) formalisms used to predict TBC. Our measurements, when compared to previous experimental data, suggest that TBC can be influenced by long wavelength, zone center modes in a material on one side of the interface as opposed to the '"vibrational mismatch"' concept assumed in the DMM; this disagreement is pronounced at high temperatures. At room temperature, we measure the ZnO/GaN TBC as 490[+150,-110] MW m-2 K-1. The disagreement among the DMM and AGF, and the experimental data at elevated temperatures, suggests a non-negligible contribution from other types of modes that are not accounted for in the fundamental assumptions of these harmonic based formalisms, which may rely on anharmonicity. Given the high quality of these ZnO/GaN interfaces, these results provide an invaluable, critical, and quantitative assessment of the accuracy of assumptions in the current state of the art computational approaches used to predict phonon TBC across interfaces.

Efficacy of an Organizational Skills Intervention for College Students With ADHD Symptomatology and Academic Difficulties.

OBJECTIVE: We sought to elucidate the effects of an organization, time management, and planning (OTMP) skills training intervention for college students reporting elevated levels of ADHD symptomatology and academic impairment. METHOD: Undergraduate participants enrolled in either the intervention ( n = 22) or comparison ( n = 15) condition in exchange for psychology course credit. Those in the intervention condition attended three weekly group meetings designed to improve organizational skills. Treatment effectiveness was evaluated by comparing pre- and postmeasurements of academic impairment, inattention, hyperactivity/impulsivity, and OTMP skills utilization. RESULTS: Intervention group participants improved significantly on ratings of inattention, hyperactivity/impulsivity, and academic impairment, relative to the comparison group. Intervention group participants also improved in their use of OTMP skills, relative to their baseline ratings. CONCLUSION: This study suggests an organizational skills intervention has the potential to ameliorating ADHD symptomatology and academic impairment among college students.

Novel Bispecific Domain Antibody to LRP6 Inhibits Wnt and R-spondin Ligand-Induced Wnt Signaling and Tumor Growth.

UNLABELLED: Aberrant WNT signaling is associated with the formation and growth of numerous human cancer types. The low-density lipoprotein receptor-related protein 6 (LRP6) is the least redundant component of the WNT receptor complex with two independent WNT ligand-binding sites. Using domain antibody (dAb) technology, a bispecific antibody (GSK3178022) to LRP6 was identified that is capable of blocking stimulation in the presence of a range of WNT and R-spondin (RSPO) ligands in vitro GSK3178022 was also efficacious in reducing WNT target gene expression in vivo, in both cancer cell line and patient-derived xenograft models, and delays tumor growth in a patient-derived RSPO fusion model of colorectal cancer. IMPLICATIONS: This article demonstrates the inhibition of a key oncogenic receptor, intractable to mAb inhibition due to multiple independent ligand interaction sites, using an innovative dAb approach. Mol Cancer Res; 14(9); 859-68. ©2016 AACR.

Dysprosium-doped cadmium oxide as a gateway material for mid-infrared plasmonics.

The interest in plasmonic technologies surrounds many emergent optoelectronic applications, such as plasmon lasers, transistors, sensors and information storage. Although plasmonic materials for ultraviolet-visible and near-infrared wavelengths have been found, the mid-infrared range remains a challenge to address: few known systems can achieve subwavelength optical confinement with low loss in this range. With a combination of experiments and ab initio modelling, here we demonstrate an extreme peak of electron mobility in Dy-doped CdO that is achieved through accurate 'defect equilibrium engineering'. In so doing, we create a tunable plasmon host that satisfies the criteria for mid-infrared spectrum plasmonics, and overcomes the losses seen in conventional plasmonic materials. In particular, extrinsic doping pins the CdO Fermi level above the conduction band minimum and it increases the formation energy of native oxygen vacancies, thus reducing their populations by several orders of magnitude. The substitutional lattice strain induced by Dy doping is sufficiently small, allowing mobility values around 500 cm(2) V(-1) s(-1) for carrier densities above 10(20) cm(-3). Our work shows that CdO:Dy is a model system for intrinsic and extrinsic manipulation of defects affecting electrical, optical and thermal properties, that oxide conductors are ideal candidates for plasmonic devices and that the defect engineering approach for property optimization is generally applicable to other conducting metal oxides.

Investigation of dry powder inhaler (DPI) resistance and aerosol dispersion timing on emitted aerosol aerodynamic particle sizing by multistage cascade impactor when sampled volume is reduced from compendial value of 4 L.

Compendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes. APSD measurements were made using the same CI systems with inhalers representing low and high flow resistance extremes (Cyclohaler® and HandiHaler® DPIs, respectively). The ratio of sample volume to internal dead space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43 to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus transfer; the higher resistance DPI completing bolus relocation to the NGI pre-separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the bolus mass was collected at this condition with the Cyclohaler® DPI. Size fractionation of the bolus from either DPI was completed within the ACI at smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler® capsule and from the HandiHaler® to the ACI system were unaffected by the different flow rise time observed in the two different flow controller systems, and the effects the ACI-based on APSD measurements were marginal.

In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.

We used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic stem and progenitor cells did not affect engraftment, reconstitution, or differentiation. Finally, using an Itgb3 knockout mouse model, we confirmed that Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.

The Word Game: an innovative strategy for assessing implicit processes in parents at risk for child physical abuse.

OBJECTIVE: Contemporary theories of child physical abuse (CPA) emphasize the proximal role of social cognitive processes (many of which are implicit in nature) in the occurrence of parental aggression. However, methods that allow for the systematic examination of implicit cognitive processes during the course of aggressive interactions are needed. To address this need, the present study was designed to examine the utility of the Word Game, an innovative procedure designed to assess implicit changes in schema accessibility during the course of an interpersonal exchange involving aggressive response options. METHODS: The game involves a series of competitive reaction time trials which are actually lexical decision making trials designed to determine the accessibility of schema throughout the game. Each parent was led to believe that they were competing against another player with whom they exchanged sound blasts of varying intensities. Participants in the present study were parents who were either low (n=50) or high (n=20) risk for CPA. RESULTS: Results revealed that high CPA risk parents behaved more aggressively than low CPA risk parents and that provocation augmented the aggressiveness of all participants. Among high CPA risk parents, positive schema became less accessible (whereas negative schema became more accessible) following lost rounds. At the conclusion of the game, high CPA risk parents reported more aggressive motives than low CPA risk parents. Further, aggressive motives significantly mediated the association between CPA risk status and aggressiveness (i.e., mean sound blast selections). CONCLUSIONS: Collectively, results support the potential utility of the Word Game as a means of advancing the study of social cognitive processes involved in parental aggression.

Activation and intrinsic gamma-secretase activity of presenilin 1.

A complex composed of presenilin (PS), nicastrin, PEN-2, and APH-1 is absolutely required for γ-secretase activity in vivo. Evidence has emerged to suggest a role for PS as the catalytic subunit of γ-secretase, but it has not been established that PS is catalytically active in the absence of associated subunits. We now report that bacterially synthesized, recombinant PS (rPS) reconstituted into liposomes exhibits γ-secretase activity. Moreover, an rPS mutant that lacks a catalytic aspartate residue neither exhibits reconstituted γ-secretase activity nor interacts with a transition-state γ-secretase inhibitor. Importantly, we demonstrate that rPS harboring mutations that cause early onset familial Alzheimer's disease (FAD) lead to elevations in the ratio of Aß42 to Aß40 peptides produced from a wild-type APP substrate and that rPS enhances the Aß42/Aß40 peptide ratio from FAD-linked mutant APP substrates, findings that are entirely consistent with the results obtained in in vivo settings. Thus, γ-secretase cleavage specificity is an inherent property of the polypeptide. Finally, we demonstrate that PEN2 is sufficient to promote the endoproteolysis of PS1 to generate the active form of γ-secretase. Thus, we conclusively establish that activated PS is catalytically competent and the bimolecular interaction of PS1 and PEN2 can convert the PS1 zymogen to an active protease.

Cascade impactor (CI) mensuration--an assessment of the accuracy and precision of commercially available optical measurement systems.

Multi-stage cascade impactors (CIs) are the preferred measurement technique for characterizing the aerodynamic particle size distribution of an inhalable aerosol. Stage mensuration is the recommended pharmacopeial method for monitoring CI "fitness for purpose" within a GxP environment. The Impactor Sub-Team of the European Pharmaceutical Aerosol Group has undertaken an inter-laboratory study to assess both the precision and accuracy of a range of makes and models of instruments currently used for optical inspection of impactor stages. Measurement of two Andersen 8-stage 'non-viable' cascade impactor "reference" stages that were representative of jet sizes for this instrument type (stages 2 and 7) confirmed that all instruments evaluated were capable of reproducible jet measurement, with the overall capability being within the current pharmacopeial stage specifications for both stages. In the assessment of absolute accuracy, small, but consistent differences (ca. 0.6% of the certified value) observed between 'dots' and 'spots' of a calibrated chromium-plated reticule were observed, most likely the result of treatment of partially lit pixels along the circumference of this calibration standard. Measurements of three certified ring gauges, the smallest having a nominal diameter of 1.0 mm, were consistent with the observation where treatment of partially illuminated pixels at the periphery of the projected image can result in undersizing. However, the bias was less than 1% of the certified diameter. The optical inspection instruments evaluated are fully capable of confirming cascade impactor suitability in accordance with pharmacopeial practice.