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1.
Heliyon ; 9(12): e22722, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38090005

RESUMO

Energy and exergy interactions in industrial systems hold meaning across physical domains. This paper builds on the notion that capturing the energy and exergy interactions of a system, while retaining physical structural context, enables fault detection and isolation. To this end, three energy graph-based visualisation methods were developed for the purpose of fault detection and isolation. This paper presents a comparative study of the three analysis methods designated the 1) distance parameter method, 2) eigenvalue decomposition method, and 3) residual method. The study utilises data from a physical lignite plant in Janschwalde, Germany, in combination with simulation data of specific faults in order to compare the sensitivity and robustness of the three methods. The comparison is done firstly in terms of detection and secondly in terms of isolation. The distance parameter and eigenvalue decomposition methods showed high sensitivity and robustness for fault detection, while the residual method showed moderate comparative performance. In terms of fault isolation, the distance parameter method showed high sensitivity and robustness, while the eigenvalue decomposition method had irregular isolation performance. The residual method isolation results proved inconclusive.

2.
PLoS One ; 18(10): e0293393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37889922

RESUMO

The coronavirus (COVID-19) pandemic had wide-ranging negative impacts on mental health. The pandemic also placed extraordinary strain on frontline workers who were required to continue working and putting themselves at risk to provide essential services at a time when their normal support mechanisms may not have been available. This paper presents an evaluation of the Time for You service, a rapidly developed and implemented intervention aimed at providing frontline workers with quick access to flexible online mental health support. Time for You provided service users with three service options: self-guided online cognitive behavioural therapy (CBT) resources; guided engagement with online CBT resources; 1-1 psychological therapy with trainee sport and exercise psychologists and trainee health psychologists. A process evaluation informed by the Consolidated Framework for Implementation Research considered service fidelity, adaptations, perceived impact, reach, barriers, and facilitators. Interviews with project managers (n = 5), delivery staff (n = 10), and service users (n = 14) explored perceptions of the service implementation and outcomes, supported by data regarding engagement with the online CBT platform (n = 217). Findings indicated that service users valued the flexibility of the service and the speed with which they were able to access support. The support offered by Trainee Psychologists was perceived to be of high quality, and the service was perceived by service users to have improved mental health and wellbeing. The rapid implementation contributed to issues regarding appropriate service user screening that led to trainee psychologists being unable to provide the service users with the support they needed as the presenting issues were outside of trainees' competencies. Overall, the findings suggest that interventions offering flexible, online psychological support to frontline workers can be an effective model for future interventions. Trainee psychologists are also able to play an important role in delivering such services when clear screening processes are in place.


Assuntos
COVID-19 , Serviços de Saúde Mental , Humanos , Saúde Mental , COVID-19/epidemiologia , Pandemias , Nível de Saúde
3.
Onderstepoort J Vet Res ; 90(1): e1-e8, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37042558

RESUMO

Neospora caninum is a coccidian parasite that occurs worldwide and is one of the most important causes of abortion, especially in cattle. However, no studies have been performed in Namibia to determine the N. caninum status in livestock. Therefore, this study aimed to determine the seroprevalence of N. caninum in cattle and the associated risk factors in the Khomas region of Namibia. A total of 736 sera were collected from cows in 32 farming establishments. These comprised 698 beef and 38 dairy cattle sera and were tested using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Questionnaires were concurrently administered to determine possible risk factors associated with N. caninum seropositivity. A total of 42 sera were positive (all beef), giving an animal-level seroprevalence rate of 5.7%. Eight of the 32 establishments had at least one positive animal, giving a herd-level seroprevalence of 25%. There was no significant association between seropositivity and the presence of dogs, jackals, history of abortions, farm size, number of cattle or average annual rainfall. The establishments with moderate to high numbers of Feliformia were 9.8 times more likely to be seropositive to N. caninum than those with none to low levels of the former (p = 0.0245). The authors concluded that the seroprevalence level of N. caninum in the Khomas region was relatively low compared with other parts of the world and that the role of Feliformia in the epidemiology of bovine neosporosis needed to be further investigated.Contribution: Serological evidence of bovine neosporosis and the associated risk factors are reported in Namibia for the first time. This study contributes to the scientific body of knowledge on N. caninum in Africa, which is currently limited.


Assuntos
Doenças dos Bovinos , Coccidiose , Neospora , Animais , Bovinos , Anticorpos Antiprotozoários/sangue , Doenças dos Bovinos/sangue , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Coccidiose/sangue , Coccidiose/epidemiologia , Coccidiose/parasitologia , Coccidiose/veterinária , Namíbia/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Feliformes
4.
Pharm Pract (Granada) ; 18(2): 1814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477433

RESUMO

BACKGROUND: Embedding pharmacists in general practice has been shown to create cost efficiencies, improve patient care and free general practitioner capacity. Consequently, there is a drive to recruit additional pharmacists to work within general practices. However, equipping pharmacists with behaviour and influencing skills may further optimise their impact. Key elements which may enhance behaviour and influencing skills include self-efficacy and resilience. OBJECTIVE: This study aimed to: 1) Assess general practice pharmacists' self-efficacy and resilience. 2) Explore differences primarily between pharmacists reporting lower and higher self-efficacy, secondarily for those reporting lower and higher scores for resilience. METHODS: All 159 NHS Greater Glasgow and Clyde general practice pharmacists were invited to complete an online survey in May 2019. The survey captured anonymised data covering: demographics; professional experience; qualifications, prescribing status and preferred learning styles. Unconscious learning needs for behavioural and influencing skills were assessed using validated tools: the new general self-efficacy scale (GSES) and short general resilience scale (GRIT). Participants' responses were differentiated by the lowest quartile and higher quartiles of GSES and GRIT scores, and analysed to identify differences. RESULTS: The survey was completed by 57% (91/159) of eligible pharmacists; mean age 38 (range 24-60) years; 91% were of white ethnicity and 89% female. The median time qualified was 14 (1-38) years and 3 (1-22) years working in general practices. Overall pharmacists scored well on the GSES, mean 25 (SD 3; 95%CI 24.4-25.6), and GRIT, mean 30 (SD 4; 95%CI 29.6-30.4), out of a maximum 32 and 40 respectively. A significant positive correlation between GSES and GRIT scores was found (Pearson's r=0.284, p=0.006). However, no significant differences were identified between pharmacists scoring in the lower and upper quartiles by GSES or GRIT. Overall respondents reported their preferred learning styles were activists (46%) or pragmatists (29%). The majority (91%) preferred blended learning methods as opposed to 38% or less for a range of online methods. CONCLUSIONS: General practice pharmacists on average scored highly for self-efficacy and resilience. Higher scores did not appear to be associated with demographic, years of practice, professional or educational experience. Prospective interventions to support those with lower scores may enhance and optimise pharmacists' effectiveness in general practice.

5.
J Alzheimers Dis ; 72(2): 455-465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31594223

RESUMO

Diffusion changes as determined by diffusion tensor imaging are potential indicators of microstructural lesions in people with mild cognitive impairment (MCI), prodromal Alzheimer's disease (AD), and AD dementia. Here we extended the scope of analysis toward subjective cognitive complaints as a pre-MCI at risk stage of AD. In a cohort of 271 participants of the prospective DELCODE study, including 93 healthy controls and 98 subjective cognitive decline (SCD), 45 MCI, and 35 AD dementia cases, we found reductions of fiber tract integrity in limbic and association fiber tracts in MCI and AD dementia compared with controls in a tract-based analysis (p < 0.05, family wise error corrected). In contrast, people with SCD showed spatially restricted white matter alterations only for the mode of anisotropy and only at an uncorrected level of significance. DTI parameters yielded a high cross-validated diagnostic accuracy of almost 80% for the clinical diagnosis of MCI and the discrimination of Aß positive MCI cases from Aß negative controls. In contrast, DTI parameters reached only random level accuracy for the discrimination between Aß positive SCD and control cases from Aß negative controls. These findings suggest that in prodromal stages of AD, such as in Aß positive MCI, multicenter DTI with prospectively harmonized acquisition parameters yields diagnostic accuracy meeting the criteria for a useful biomarker. In contrast, automated tract-based analysis of DTI parameters is not useful for the identification of preclinical AD, including Aß positive SCD and control cases.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/diagnóstico , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/diagnóstico , Idoso , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Estudos de Coortes , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/patologia , Masculino , Pessoa de Meia-Idade , Placa Amiloide/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Substância Branca/patologia
6.
PLoS One ; 14(5): e0216528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067253

RESUMO

BACKGROUND: Complications of diverticular disease are increasingly common, possibly linked to increasing obesity. Visceral fat could contribute to the development of symptomatic diverticular disease through its pro-inflammatory effects. OBJECTIVE: The study had 2 aims. A) to develop a semi-automated algorithm to measure abdominal adipose tissue from 2-echo magnetic resonance imaging (MRI) data; B) to use this to determine if visceral fat was associated with bowel symptoms and inflammatory markers in patients with symptomatic and asymptomatic diverticular disease. DESIGN: An observational study measuring visceral fat using MRI together with serum adiponectin, leptin, stool calprotectin and patient-reported somatisation and bowel habit. SETTING: Medical and imaging research centres of a university hospital. PARTICIPANTS: MRI scans were performed on 55 patients after an overnight fast measuring abdominal subcutaneous and visceral adipose tissue volumes together with small bowel water content (SBWC). Blood and stool samples were collected and patients kept a 2 week stool diary and completed a somatisation questionnaire. MAIN OUTCOME MEASURES: Difference in the volume of visceral fat between symptomatic and asymptomatic patients. RESULTS: There were no significant differences in visceral (p = 0.98) or subcutaneous adipose (p = 0.60) tissue between symptomatic and asymptomatic patients. However measured fat volumes were associated with serum adipokines. Adiponectin showed an inverse correlation with visceral adipose tissue (VAT) (Spearman ρ = -0.5, p = 0.0003), which correlated negatively with SBWC (ρ = -0.3, p = 0.05). Leptin correlated positively with subcutaneous adipose tissue (ρ = 0.8, p < 0.0001). Overweight patients (BMI > 25 kgm-2) showed a moderate correlation between calprotectin and VAT (ρ = 0.3, p = 0.05). Somatization scores were significantly higher in symptomatic patients (p < 0.0003). CONCLUSIONS: Increasing visceral fat is associated with lower serum adiponectin and increased faecal calprotectin suggesting a pro-inflammatory effect which may predispose to the development of complications of diverticulosis.


Assuntos
Adiponectina/sangue , Índice de Massa Corporal , Divertículo/patologia , Fezes/química , Gordura Intra-Abdominal/fisiopatologia , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Divertículo/epidemiologia , Divertículo/metabolismo , Feminino , Humanos , Resistência à Insulina , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
7.
Bioorg Med Chem Lett ; 27(18): 4370-4376, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28830649

RESUMO

Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model. In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients.


Assuntos
Imidazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , TYK2 Quinase/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Imidazóis/síntese química , Imidazóis/química , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade , TYK2 Quinase/metabolismo
8.
J Nurs Educ ; 56(5): 292-294, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28467558

RESUMO

BACKGROUND: Schools of nursing have moved to multiple choice test questions to help prepare students for licensure and practice. However, students can buy test banks to help them "get through" nursing school. Accurate assessment of nursing students' knowledge and judgment comprises access to test banks. METHOD: The purpose of this exploratory study was to gain an understanding about nursing faculty's knowledge concerning test bank security issues, to assess whether publishers were aware of this issue, and vendor's reasons for supplying test banks to students. RESULTS: Overall, the results indicated that the majority of faculty were unaware of student access to test banks, and although most do not use test banks verbatim, general consensus existed that test bank security is a concern. CONCLUSION: Implications include increasing faculty awareness of test bank access by students, supporting educators to develop their own test bank items, and promoting security of all examinations. [J Nurs Educ. 2017;56(5):292-294.].


Assuntos
Bases de Dados como Assunto , Educação em Enfermagem , Avaliação Educacional , Atitude do Pessoal de Saúde , Comércio , Docentes de Enfermagem , Humanos , Internet , Inquéritos e Questionários
9.
Explore (NY) ; 13(3): 207-217, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28336055

RESUMO

CONTEXT: Posttraumatic stress disorder (PTSD) is a serious health concern. Current evidence-based treatments for PTSD are efficacious; however, they are not appropriate or tolerated by everyone who needs them. Alternative treatment approaches are needed. Shamanic healing is one such therapy that may potentially be beneficial but no systematic research has been conducted on it for PTSD. OBJECTIVE: The objectives of the case series are to (1) develop a structured replicable shamanic treatment plan for veterans with posttraumatic stress disorder (PTSD); (2) collect preliminary data on PTSD-related outcomes, and (3) explore the feasibility and potential for adverse events of the plan. DESIGN: Case series. SETTING: Clinical. PATIENTS OR OTHER PARTICIPANTS: Veterans with PTSD. INTERVENTION: Shamanic healing. MAIN OUTCOME MEASURE(S): PTSD symptoms, quality of life, and piritual wellness. RESULTS: A semi-structured shamanic healing protocol was created with the following components: rapport building, power animal retrieval, extraction, compassionate spirit release, curse unraveling, soul retrieval, forgiveness/cord-cutting, aspect maturing/soul rematrixing, and divination. Six veterans enrolled in the study (mean age = 49.3 ± 13.1). Qualitative descriptions of the participants, their histories, and effects from the intervention are reported. Preliminary data was collected on PTSD-related outcomes. The protocol was found feasible and acceptable and recommendations for its future use are suggested. Future research is warranted and needed to evaluate the efficacy of shamanic healing as a potential therapy for veterans with PTSD.


Assuntos
Qualidade de Vida , Xamanismo , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Espiritualidade , Resultado do Tratamento , Veteranos
10.
Am J Infect Control ; 45(5): 569-571, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28063726

RESUMO

The objective of this study was to determine understanding of bed bathing practices over time after the implementation of a standardized bed bathing protocol. An online survey addressing bathing practices was administered preintervention and 6 and 18 months postintervention to all nurses and technicians caring for adult patients. Survey responses suggested that the intervention resulted in sustained understanding of the standardized bed bathing protocol.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Banhos/métodos , Clorexidina/análogos & derivados , Desinfecção/métodos , Pesquisa sobre Serviços de Saúde , Clorexidina/administração & dosagem , Estudos Transversais , Hospitais , Humanos , Inquéritos e Questionários
11.
Int J Lang Commun Disord ; 52(4): 514-527, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27813256

RESUMO

BACKGROUND: Effective co-practice is essential to deliver services for children with speech, language and communication needs (SLCN). The necessary skills, knowledge and resources are distributed amongst professionals and agencies. Co-practice is complex and a number of barriers, such as 'border disputes' and poor awareness of respective priorities, have been identified. However social-relational aspects of co-practice have not been explored in sufficient depth to make recommendations for improvements in policy and practice. Here we apply social capital theory to data from practitioners: an analytical framework with the potential to move beyond descriptions of socio-cultural phenomena to inform change. AIMS: Co-practice in a local authority site was examined to understand: (1) the range of social capital relations extant in the site's co-practice; (2) how these relations affected the abilities of the network to collaborate; (3) whether previously identified barriers to co-practice remain; (4) the nature of any new complexities that may have emerged; and (5) how inter-professional social capital might be fostered. METHODS & PROCEDURES: A qualitative case study of SLCN provision within one local authority in England and its linked NHS partner was completed through face-to-face semi-structured interviews with professionals working with children with SLCN across the authority. Interviews, exploring barriers and facilitators to interagency working and social capital themes, were transcribed, subjected to thematic analysis using iterative methods and a thematic framework derived. OUTCOMES & RESULTS: We identified a number of characteristics important for the effective development of trust, reciprocity and negotiated co-practice at different levels of social capital networks: macro-service governance and policy; meso-school sites; and micro-intra-practitioner knowledge and skills. Barriers to co-practice differed from those found in earlier studies. Some negative aspects of complexity were evident, but only where networked professionalism and trust was absent between professions. Where practitioners embraced and services and systems enabled more fluid forms of collaboration, then trust and reciprocity developed. CONCLUSIONS & IMPLICATIONS: Highly collaborative forms of co-practice, inherently more complex at the service governance, macro-level, bring benefits. At the meso-level of the school and support team network there was greater capacity to individualize co-practice to the needs of the child. Capacity was increased at the micro-level of knowledge and skills to harness the overall resource distributed amongst members of the inter-professional team. The development of social capital, networks of trust across SLCN support teams, should be a priority at all levels-for practitioners, services, commissioners and schools.


Assuntos
Linguagem Infantil , Comunicação , Comportamento Cooperativo , Prestação Integrada de Cuidados de Saúde/organização & administração , Comunicação Interdisciplinar , Transtornos da Linguagem/reabilitação , Equipe de Assistência ao Paciente/organização & administração , Capital Social , Distúrbios da Fala/reabilitação , Fala , Adolescente , Fatores Etários , Atitude do Pessoal de Saúde , Criança , Inglaterra , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Transtornos da Linguagem/diagnóstico , Transtornos da Linguagem/psicologia , Papel Profissional , Pesquisa Qualitativa , Serviços de Saúde Escolar/organização & administração , Fatores Socioeconômicos , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/psicologia , Patologia da Fala e Linguagem/organização & administração , Medicina Estatal/organização & administração
12.
Burns ; 41(4): 727-34, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25535118

RESUMO

INTRODUCTION: Returning to school can be a major step for burn-injured children, their family, and staff and pupils at the receiving school. Previous literature has recognised the difficulties children may face after a significant injury and factors that may influence a successful reintegration. AIM: A regional paediatric burns service recognised that some patients were experiencing difficulties in returning to school. A baseline audit confirmed this and suggested factors that hindered or facilitated this process, initiating the development of a school reintegration programme (SRP). Since the programme's development in 2009, it has been audited annually. The aim of this paper was to evaluate the impact of the SRP by presenting data from the 2009 to 2011 audits. METHOD: For the baseline audit, the burn care team gathered information from clinical records (age, gender, total body surface area burned (TBSA), skin grafting and length of stay) and telephone interviews with parents and teachers of the school returners. For the re-audits, the same information was gathered from clinical records and feedback questionnaires. RESULTS: Since its introduction, the mean length of time from discharge to return to school has dropped annually for those that opted into the programme, when compared to the baseline by 62.3% (53 days to 20 days). Thematic analysis highlights positive responses to the programme from all involved. Increased awareness and feeling supported were amongst the main themes to emerge. CONCLUSIONS: Returning to school after a significant burn injury can be challenging for all involved, but we hypothesise that outreach interventions in schools by burns services can have a positive impact on the time it takes children to successfully reintegrate.


Assuntos
Queimaduras/reabilitação , Instituições Acadêmicas , Adolescente , Superfície Corporal , Queimaduras/psicologia , Queimaduras/cirurgia , Criança , Auditoria Clínica , Feminino , Humanos , Masculino , Alta do Paciente , Transplante de Pele , Ajustamento Social , Inquéritos e Questionários , Fatores de Tempo
15.
Zoo Biol ; 33(2): 121-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24519804

RESUMO

Little is known of spotted-necked otter behavior, particularly in lentic ecosystems. In 2005, the Association of Zoos and Aquariums (AZA) selected this species for management under the Small Carnivore Taxonomic Regional Collection Plan (SCTAG). In 2012, the AZA Otter group recommended this species for Red SSP status. As a result of the paucity of information on natural behaviors and the requirement of thoroughly understanding a species' behavior to properly manage ex-situ populations this study was initiated. Behavioral data was recorded on Rubondo Island National Park, Tanzania between 2006 and 2009. Data was collected on habitat use as well as general behavior. Additionally, a complete catalogue of observed behaviors was maintained for future ethogram construction. Latrines, where scat is deposited, were predominantly located on projections and scattered in 20 m areas. The majority of latrines were located along forest edge habitats. Females routinely used key core areas for denning and extensive intra- and inter-sex overlapping of ranges was evident. Forest-edge habitat was used for denning; foraging and resting occurred along both forest-edge and emergent wetland shorelines. Behavioral results indicate this species is cathemeral on RINP. Average group size recorded was 1.99 with a range of 1-12. Group composition consisted of singletons or females with young. These basic groups often coalesced into packs which occasionally joined to form temporary larger schools. The results of this study will provide valuable information for the design and implementation of ex-situ spotted-necked otter management in the future.


Assuntos
Comportamento Animal/fisiologia , Ecossistema , Lontras/fisiologia , Animais , Conservação dos Recursos Naturais , Feminino , Masculino , Densidade Demográfica , Tanzânia
16.
Eur J Med Chem ; 67: 175-87, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23867602

RESUMO

A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as psoriasis and inflammatory bowel diseases (IBD), by selective targeting of TYK2. Hit triage, following a high-throughput screen for TYK2 inhibitors, revealed pyridine 1 as a promising starting point for lead identification. Initial expansion of 3 separate regions of the molecule led to eventual identification of cyclopropyl amide 46, a potent lead analog with good kinase selectivity, physicochemical properties, and pharmacokinetic profile. Analysis of the binding modes of the series in TYK2 and JAK2 crystal structures revealed key interactions leading to good TYK2 potency and design options for future optimization of selectivity.


Assuntos
Inibidores de Proteínas Quinases/farmacologia , TYK2 Quinase/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , TYK2 Quinase/metabolismo
17.
J Med Chem ; 56(11): 4521-36, 2013 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-23668484

RESUMO

Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead molecule 3. We used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 3. Further optimization eventually led to compound 37 that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, compound 37 showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.


Assuntos
4-Aminopiridina/análogos & derivados , 4-Aminopiridina/síntese química , Aminopiridinas/síntese química , Benzamidas/síntese química , TYK2 Quinase/antagonistas & inibidores , 4-Aminopiridina/farmacocinética , 4-Aminopiridina/farmacologia , Administração Oral , Aminopiridinas/farmacocinética , Aminopiridinas/farmacologia , Animais , Benzamidas/farmacocinética , Benzamidas/farmacologia , Disponibilidade Biológica , Cristalografia por Raios X , Interferon gama/antagonistas & inibidores , Interferon gama/biossíntese , Interleucina-12/metabolismo , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 3/antagonistas & inibidores , Camundongos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Ligação Proteica , Ratos , Fator de Transcrição STAT4/antagonistas & inibidores , Estereoisomerismo , Relação Estrutura-Atividade
18.
Work ; 41 Suppl 1: 1994-2000, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22317009

RESUMO

Accurate sound source localization has advantages for the performance of work by humans. The ability to accurately localize sound sources contributes to perception, decision making and task performance. Two studies were conducted to investigate the prevalence of accurate sound source localization and the enhancement that spatially separated sound source locations can have on speech perception. The first study was conducted to characterize the ability to detect the location of horizontal plane sound sources. A sample of 117 participants with the hearing capacity within the normal limits participated in the study. The results indicated that sound sources located towards the front of the participant were identified more frequently than those sound sources located towards the rear positions. Based on the results found in the first study, a second study was conducted to assess performance within a listening task. Three different spatial configurations were used to assess if similar trends in performance translated to sound sources through headphones. Fifteen research participants performed a Coordinated Response Measure (CRM) task requiring the identification of a speech phrase and its associated information for a diotic configuration and two different spatial sound source configurations. Performance measured for the diotic configuration was significantly (p(0.05) less than for the two spatial configurations. The current studies indicate distinct advantages of utilizing localized sound sources to present auditory signal and speech to listeners.


Assuntos
Localização de Som/fisiologia , Adulto , Feminino , Testes Auditivos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , África do Sul , Adulto Jovem
19.
Respir Care ; 57(4): 537-43, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22005904

RESUMO

BACKGROUND: Head of bed elevation ≥ 30° reduces ventilator-associated pneumonia in mechanically ventilated patients, but adherence is variable and difficult to monitor continuously. Unlike many clinical variables, head of bed elevation is not electronically displayed or monitored with audible alarms. HYPOTHESIS: Continuous monitoring of head of bed elevation with audible alerts and visual cues when the elevation is < 30° will improve adherence by 15%. METHODS: Head of bed elevation was continuously monitored and recorded on a central monitoring station and displayed on the bedside monitor of 16 of 24 medical intensive care unit beds. Manual bedside checks were performed twice daily at varying times. RESULTS: Continuous head of bed angle was available from 98 of 313 (31%) patient beds over a 7.5 month period, representing 322 of 1,373 mechanical ventilator days (24%). Continuous monitoring was performed for 7,720 hours, 5,542 hours with the data displayed on bedside monitors and 2,178 hours with the data available only from central monitors. Head of bed elevation was ≥ 30° for 76% of the hours when the data were displayed on bedside monitors, and for 61% of hours when it was not (P < .001, odds ratio = 2.3, 95% CI 2.0-2.6). Intermittent bedside checks for head of bed elevation ≥ 30° found 97 ± 2% adherence. CONCLUSIONS: Real-time monitoring of head of bed elevation is feasible, and when combined with audible alarms and visual cues, improves ≥ 30° elevation adherence. Intermittent bedside checks over-estimate actual adherence.


Assuntos
Unidades de Terapia Intensiva , Monitorização Fisiológica/instrumentação , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Alarmes Clínicos , Sinais (Psicologia) , Apresentação de Dados , Humanos , Monitorização Fisiológica/métodos , Estudos Prospectivos
20.
J Midwifery Womens Health ; 56(1): 75-80, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21323854

RESUMO

INTRODUCTION: A pilot test of a computer-tailored intervention designed to promote positive health behaviors during pregnancy among a low-income population across multiple ethnic groups was conducted. METHODS: Intervention content, based on the transtheoretical model, offered pregnant women assistance with smoking cessation, stress management, and increasing fruit and vegetable consumption. Pregnant women (N = 87) were recruited from federally qualified health centers. After completing the intervention, women answered a 16-item evaluation. RESULTS: Participants rated the program very positively, with 89.7% to 95.5% of participants agreeing or strongly agreeing with all evaluation items. For example, 95.4% of respondents reported that the program could help them be healthier, that they learned new information, and that the program was designed for pregnant women like themselves. Additionally, the majority of participants (92%) reported that they would recommend the program to a friend. There were no significant differences in the ratings based on demographic characteristics of the participants. Qualitative responses support acceptability for the program. Further, assessments before and after completion of the program indicated an increase in intention to make behavioral changes. DISCUSSION: With acceptability and feasibility confirmed, the next steps are to test efficacy and consequently to distribute the program to populations of underserved pregnant women.


Assuntos
Dieta/normas , Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Área Carente de Assistência Médica , Estresse Psicológico/prevenção & controle , Adolescente , Adulto , Instrução por Computador , Etnicidade , Feminino , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Projetos Piloto , Gravidez , Abandono do Hábito de Fumar , Adulto Jovem
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