Second Year Results from Razor C.O.A.C.H.

In this paper, we present the results of a random assignment evaluation on the Razor C.O.A.C.H. (Creating Opportunities for Arkansan’s Career Hopes) program. As the program started in the 2012-13 school year, this evaluation analyzes the impact of the program in its second year of operation and includes two cohorts of students. The focus of the comprehensive evaluation is the impacts of the program on students’ academic outcomes, short-term noncognitive outcomes, short-term college and career readiness outcomes, and post-secondary outcomes

Engineering Agatoxin, a Cystine-Knot Peptide from Spider Venom, as a Molecular Probe for In Vivo Tumor Imaging

Background: Cystine-knot miniproteins, also known as knottins, have shown great potential as molecular scaffolds for the development of targeted therapeutics and diagnostic agents. For this purpose, previous protein engineering efforts have focused on knottins based on the Ecballium elaterium trypsin inhibitor (EETI) from squash seeds, the Agouti-related protein (AgRP) neuropeptide from mammals, or the Kalata B1 uterotonic peptide from plants. Here, we demonstrate that Agatoxin (AgTx), an ion channel inhibitor found in spider venom, can be used as a molecular scaffold to engineer knottins that bind with high-affinity to a tumor-associated integrin receptor. Methodology/Principal Findings: We used a rational loop-grafting approach to engineer AgTx variants that bound to α β integrin with affinities in the low nM range. We showed that a disulfide-constrained loop from AgRP, a structurally-related knottin, can be substituted into AgTx to confer its high affinity binding properties. In parallel, we identified amino acid mutations required for efficient in vitro folding of engineered integrin-binding AgTx variants. Molecular imaging was used to evaluate in vivo tumor targeting and biodistribution of an engineered AgTx knottin compared to integrin-binding knottins based on AgRP and EETI. Knottin peptides were chemically synthesized and conjugated to a near-infrared fluorescent dye. Integrin-binding AgTx, AgRP, and EETI knottins all generated high tumor imaging contrast in U87MG glioblastoma xenograft models. Interestingly, EETI-based knottins generated significantly lower non-specific kidney imaging signals compared to AgTx and AgRP-based knottins. Conclusions/Significance: In this study, we demonstrate that AgTx, a knottin from spider venom, can be engineered to bind with high affinity to a tumor-associated receptor target. This work validates AgTx as a viable molecular scaffold for protein engineering, and further demonstrates the promise of using tumor-targeting knottins as probes for in vivo molecular imaging

Crystal Structure of (E)-2-[(2- bromo-3-pyridyl)methylidene]-6-methoxy-3,4-dihydronaphthalen-1-one and 3-[(E)-(6- methoxy-3,4-dihydronaphth-2-oylidene)methyl]-1H-pyridin-2-one

The title compounds C17H14BrNO2, (I), and C17H15NO3, (II), were obtained from the reaction of 6-meth­oxy-3,4-di­hydro-2H-naphthalen-1-one and 2-bromo­nicotinaldehyde in ethanol. Compound (I) was the expected product and compound (II) was the oxidation product from air exposure. In the crystal structure of compound (I), there are no short contacts or hydrogen bonds. The structure does display [pi]-[pi] inter­actions between adjacent benzene rings and adjacent pyridyl rings. Compound (II) contains two independent mol­ecules, A and B, in the asymmetric unit; both are non-planar, the dihedral angles between the meth­oxy­benzene and 1H-pyridin-2-one mean planes being 35.07 (9)° in A and 35.28 (9)°in B. In each mol­ecule, the 1H-pyridin-2-one unit participates in inter­molecular N-H...O hydrogen bonding to another mol­ecule of the same type (A to A or B to B). The structure also displays [pi]-[pi] inter­actions between the pyridyl and the benzene rings of non-equivalent mol­ecules (viz., A to B and B to A)

Semi-field evaluation of freestanding transfluthrin passive emanators and the BG sentinel trap as a "push-pull control strategy" against Aedes aegypti mosquitoes

Spatial repellents that drive mosquitoes away from treated areas, and odour-baited traps, that attract and kill mosquitoes, can be combined and work synergistically in a push-pull system. Push-pull systems have been shown to reduce house entry and outdoor biting rates of malaria vectors and so have the potential to control other outdoor biting mosquitoes such as Aedes aegypti that transmit arboviral diseases. In this study, semi-field experiments were conducted to evaluate whether a push-pull system could be used to reduce bites from Aedes mosquitoes.; The push and pull under investigation consisted of two freestanding transfluthrin passive emanators (FTPE) and a BG sentinel trap (BGS) respectively. The FTPE contained hessian strips treated with 5.25 g of transfluthrin active ingredient. The efficacies of FTPE and BGS alone and in combination were evaluated by human landing catch in a large semi-field system in Tanzania. We also investigated the protection of FTPE over six months. The data were analyzed using generalized linear mixed models with binomial distribution.; Two FTPE had a protective efficacy (PE) of 61.2% (95% confidence interval (CI): 52.2-69.9%) against the human landing of Ae. aegypti. The BGS did not significantly reduce mosquito landings; the PE was 2.1% (95% CI: -2.9-7.2%). The push-pull provided a PE of 64.5% (95% CI: 59.1-69.9%). However, there was no significant difference in the PE between the push-pull and the two FTPE against Ae. aegypti (P = 0.30). The FTPE offered significant protection against Ae. aegypti at month three, with a PE of 46.4% (95% CI: 41.1-51.8%), but not at six months with a PE of 2.2% (95% CI: -9.0-14.0%).; The PE of the FTPE and the full push-pull are similar, indicative that bite prevention is primarily due to the activity of the FTPE. While these results are encouraging for the FTPE, further work is needed for a push-pull system to be recommended for Ae. aegypti control. The three-month protection against Ae. aegypti bites suggests that FTPE would be a useful additional control tool during dengue outbreaks, that does not require regular user compliance

Compassion, stigma, and professionalism among emergency personnel responding to the opioid crisis: An exploratory study in New Hampshire, USA.

OBJECTIVE: Drug overdoses are the leading cause of death in the United States for those under 50 years of age, and New Hampshire has been disproportionately affected, resulting in increased encounters with the emergency response system. The ensuing impact on emergency personnel has received little attention. The present study aimed to explore the experiences and perspectives of emergency personnel responding to the opioid crisis in NH, with a focus on their views toward people who use opioids. METHODS: Thirty-six emergency personnel (emergency department clinicians, n = 18; emergency medical service providers, n = 6; firefighters, n = 6; and police officers, n = 6) in 6 New Hampshire counties were interviewed about their experiences responding to overdoses and their perspectives on individuals who use opioids. Directed content analysis was used to identify themes in the transcribed, semistructured interviews. The results were reviewed for consensus. RESULTS: Several categories of themes were identified among emergency personnel's accounts of their overdose response experiences and perspectives, including varied degrees of compassion and stigma toward people who use opioids; associations between compassion or stigma and policy- and practice-related themes, such as prehospital emergency care and the role of emergency departments (EDs); and primarily among personnel expressing compassion, a sense of professional responsibility that outweighed personal biases. CONCLUSIONS: Despite the magnitude of the ongoing opioid crisis, some emergency personnel in New Hampshire have sustained or increased their compassion for people who use opioids. Others' perspectives remain or have become increasingly stigmatizing. The associations of compassion and stigma with various policy- and practice-related themes warrant further investigation

Water‐borne and plasma corticosterone are not correlated in spotted salamanders

Water‐borne hormone measurement is a noninvasive method suitable for amphibians of all sizes that are otherwise difficult to sample. For this method, containment‐water is assayed for hormones released by the animal. Originally developed in fish, the method has expanded to amphibians, but requires additional species‐specific validations. We wanted to determine physiological relevance of water‐borne corticosterone in spotted salamanders (Ambystoma maculatum) by comparing concentrations to those taken using established corticosterone sampling methods, such as plasma. Using a mixture of field and laboratory studies, we compared water‐borne corticosterone levels to other traditional methods of sampling corticosterone for spotted salamander larvae, metamorphs, and adults. Despite multiple attempts, and detecting differences between age groups, we found no correlations between water‐borne and plasma corticosterone levels in any age group. Water‐borne sampling measures a rate of release; whereas plasma is the concentration circulating in the blood. The unique units of measurement may inherently prevent correlations between the two. These two methods may also require different interpretations of the data and the physiological meaning. We also note caveats with the method, including how to account for differences in body size and life history stages. Collectively, our results illustrate the importance of careful validation of water‐borne hormone levels in each species in order to understand its physiological significance

Water‐borne and Plasma Corticosterone are not Correlated in Spotted Salamanders

Water‐borne hormone measurement is a noninvasive method suitable for amphibians of all sizes that are otherwise difficult to sample. For this method, containment‐water is assayed for hormones released by the animal. Originally developed in fish, the method has expanded to amphibians, but requires additional species‐specific validations. We wanted to determine physiological relevance of water‐borne corticosterone in spotted salamanders (Ambystoma maculatum) by comparing concentrations to those taken using established corticosterone sampling methods, such as plasma. Using a mixture of field and laboratory studies, we compared water‐borne corticosterone levels to other traditional methods of sampling corticosterone for spotted salamander larvae, metamorphs, and adults. Despite multiple attempts, and detecting differences between age groups, we found no correlations between water‐borne and plasma corticosterone levels in any age group. Water‐borne sampling measures a rate of release; whereas plasma is the concentration circulating in the blood. The unique units of measurement may inherently prevent correlations between the two. These two methods may also require different interpretations of the data and the physiological meaning. We also note caveats with the method, including how to account for differences in body size and life history stages. Collectively, our results illustrate the importance of careful validation of water‐borne hormone levels in each species in order to understand its physiological significance

A qualitative study examining the benefits and challenges of incorporating patient-reported outcome substance use and mental health questionnaires into clinical practice to improve outcomes on the HIV care continuum.

BACKGROUND: Inadequate identification and treatment of substance use (SU) and mental health (MH) disorders hinders retention in HIV care. The objective of this study was to elicit stakeholder input on integration of SU/MH screening using computer-assisted patient-reported outcomes (PROs) into clinical practice. METHODS: We conducted semi-structured interviews with HIV-positive patients who self-reported SU/MH symptoms on a computer-assisted PROs (n = 19) and HIV primary care providers (n = 11) recruited from an urban academic HIV clinic. Interviews were audio-recorded and transcribed. We iteratively developed codes and organized key themes using editing style analysis. RESULTS: Two themes emerged: (1) Honest Disclosure: Some providers felt PROs might improve SU/MH disclosure; more were concerned that patients would not respond honestly if their provider saw the results. Patients were also divided, stating PROs could help overcome stigma but that it could be harder to disclose SU/MH to a computer versus a live person. (2) Added Value in the Clinical Encounter: Most providers felt PROs would fill a practice gap. Patients had concerns regarding confidentiality but indicated PROs would help providers take better care of them. CONCLUSIONS: Both patients and providers indicated that PROs are potentially useful clinical tools to improve detection of SU/MH. However, patients and providers expressed conflicting viewpoints about disclosure of SU/MH using computerized PROs. Future studies implementing PROs screening interventions must assess concerns over confidentiality and honest disclosure of SU/MH to understand the effectiveness of PROs as a clinical tool. More research is also needed on patient-centered integration of the results of PROs in HIV care

Assessment of Obstetric and Neonatal Health Services in Developing Country Health Facilities

OBJECTIVE: To describe the staffing and availability of medical equipment and medications and the performance of procedures at health facilities providing maternal and neonatal care at African, Asian, and Latin American sites participating in a multicenter trial to improve emergency obstetric/neonatal care in communities with high maternal and perinatal mortality. STUDY DESIGN: In 2009, prior to intervention, we surveyed 136 hospitals and 228 clinics in 7 sites in Africa, Asia, and Latin America regarding staffing, availability of equipment/medications, and procedures including cesarean section. RESULTS: The coverage of physicians and nurses/midwives was poor in Africa and Latin America. In Africa, only 20% of hospitals had full-time physicians. Only 70% of hospitals in Africa and Asia had performed cesarean sections in the last 6 months. Oxygen was unavailable in 40% of African hospitals and 17% of Asian hospitals. Blood was unavailable in 80% of African and Asian hospitals. CONCLUSIONS: Assuming that adequate facility services are necessary to improve pregnancy outcomes, it is not surprising that maternal and perinatal mortality rates in the areas surveyed are high. The data presented emphasize that to reduce mortality in these areas, resources that result in improved staffing and sufficient equipment, supplies, and medication, along with training, are required.Fil: Manasyan, Albert. Centre for Infectious Disease Zambia; Zambia. University of Alabama at Birmingahm; Estados UnidosFil: Saleem, Sarah. Aga Khan University; PakistánFil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Althabe, Fernando. Instituto de Efectividad Clínica y Política de Salud. Departamento de Investigación en Salud Madre e Infantil. Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pasha, Omrana. Aga Khan University; PakistánFil: Chomba, Elwyn. Centre for Infectious Disease Zambia; Zambia. University of Alabama at Birmingahm; Estados Unidos. University of Zambia; ZambiaFil: Goudar, Shivaprasad S.. KLE; IndiaFil: Patel, Archana. Indira Gandhi Government Medical College; IndiaFil: Esamai, Fabian. Moi University; KeniaFil: Garces, Ana. Francisco Marroquin University; GuatemalaFil: Kodkany, Bhala. KLE; IndiaFil: Belizan, Jose. Instituto de Efectividad Clínica y Política de Salud. Departamento de Investigación en Salud Madre e Infantil. Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: McClure, Elizabeth M.. Research Triangle Institute; Estados UnidosFil: Derman, Richard J.. Christiana Health Care; Estados UnidosFil: Hibberd, Patricia. Indiana University; Estados UnidosFil: Liechty, Edward A.. Massachusetts General Hospital for Children; Estados UnidosFil: Hambidge, K. Michael. State University of Colorado Boulder; Estados UnidosFil: Carlo, Waldemar A.. Centre for Infectious Disease Zambia; ZambiaFil: Buekens, Pierre. Tulane School of Public Health and Tropical Medicine; Estados UnidosFil: Moore, janet. Research Triangle Institute; Estados UnidosFil: Wright, Linda L.. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Goldenberg, Robert L.. Columbia University; Estados Unido