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1.
Artigo em Inglês | MEDLINE | ID: mdl-31936798

RESUMO

SELPHI involves two interventions: (A) It provides one HIV self-testing (HIVST) kit; (B) It offers 3-monthly repeat HIVST kits if participants report ongoing risk. A logic model underpinned by the Behaviour Change Wheel informed the design of the intervention. SELPHI recruited 10,135 cis-men and trans people in England and Wales, all reporting anal sex with a man. This paper explores how the interventions were experienced and the pathways to impact for different groups of trial participants. In-depth interviews with 37 cis-men who have sex with men (MSM) were used to inductively categorise participants based on sexual and HIV testing histories. Themes relating to intervention experiences and impacts were mapped onto SELPHI-hypothesised intermediate outcomes to consider intervention impacts. Three groups were identified: 'Inexperienced testers' engaged with SELPHI to overcome motivational and social and physical opportunity testing barriers. For 'pro self-testers', testing frequency was constrained by psychological and social barriers and lack of opportunity. 'Opportunistic adopters' engaged in HIVST for novelty and convenience. Perceived impacts for inexperienced testers were most closely aligned with the logic model, but for opportunistic adopters there was little evidence of impact. Distinctive groups were discernible with divergent intervention experiences. Using COM-B as a model for understanding behaviour change in relation to HIVST, our results indicate how HIVST interventions could be adapted to respond to different needs based on the target population's demographic and behavioural features.

2.
Vaccine ; 37(43): 6518-6525, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31519446

RESUMO

Trypsin is one of the essential raw materials used in the manufacturing of biopharmaceutical products. As an animal derived product, it can potentially carry a serious risk of contamination with adventitious agents that can result in production shut down and lost product. To mitigate these risks, several methods are currently being used in the industry to remove contamination including physical and chemical methods. Ultraviolet-C (UVC) light is known to inactivate adventitious agents that are resistant to physical and chemical methods and could be a secondary barrier strategy. In this study, we investigated the effect of UVC irradiation on the activity and structure of trypsin. Extreme doses of UVC light were applied to trypsin using a collimated beam apparatus. The effect of UVC light on trypsin enzymatic activity was measured using a colorimetric activity assay and the effect on structure was analyzed by spectrophotometry, gel electrophoresis, and mass spectrometry. To broaden the scope, the effect of UVC light on the activity of two additional enzymes, lysozyme and ß-galactosidase, was also examined. At high doses of UVC light, changes to protein structure and protein fragmentation resulted in decreased trypsin activity. However, minimal damage was observed at doses applicable to inactivating adventitious agents, making UVC a feasible treatment for viral inactivation of trypsin products.

3.
BMC Infect Dis ; 19(1): 699, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391003

RESUMO

BACKGROUND: The SELPHI study (An HIV Self-Testing Public Health Intervention) is an online randomised controlled trial (RCT) of HIV self-testing (HIVST). The aim of this study was to assess the feasibility of recruiting UK men who have sex with men (cis and trans) and trans women who have sex with men to the SELPHI pilot, and the acceptability of the HIVST intervention used among those randomised to receive a kit. METHODS: A mixed-methods approach to assessing trial feasibility and intervention acceptability was taken, using quantitative data from advertising sources and RCT surveys alongside qualitative data from a nested sub-study. RESULTS: Online recruitment and intervention delivery was feasible. The recruitment strategy led to the registration of 1370 participants of whom 76% (1035) successfully enrolled and were randomised 60/40 to baseline testing vs no baseline testing. Advertising platforms performed variably. Reported HIVST kit use increased from 83% at two weeks to 96% at three months. Acceptability was very high across all quantitative measures. Participants described the instructions as easy to use, and the testing process as simple. The support structures in SELPHI were felt to be adequate. Described emotional responses to HIVST varied. CONCLUSIONS: Recruiting to a modest sized HIVST pilot RCT is feasible, and the recruitment, intervention and HIVST kit were acceptable. Research on support needs of individuals with reactive results is warranted.


Assuntos
Infecções por HIV/diagnóstico , Homossexualidade Masculina , Marketing de Serviços de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Pessoas Transgênero , Adolescente , Adulto , Inglaterra , Estudos de Viabilidade , Infecções por HIV/psicologia , Inquéritos Epidemiológicos , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Autocuidado , Minorias Sexuais e de Gênero , Pessoas Transgênero/psicologia , País de Gales
4.
Nanotechnology ; 30(33): 335706, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31026844

RESUMO

Phase-change random access memory is a promising approach to non-volatile memory. However, the inability to secure consistent, reliable switching on a nanometre scale may limit its practical use for high density applications. Here, we report on the switching behaviour of PCRAM cells comprised of single crystalline Ge9Sb1Te5 (GST) nanowires. We show that device switching is dominated by the contacts and does not result in a resistance change within the bulk of the wire. For the devices studied, the typical contact resistance was ∼30 kΩ, whereas the resistance of the GST channel was 1.8 kΩ. The applied voltage was predominately dropped across the passivating oxide on the surface of the GST nanowires, resulting in local resistive switching at the contacts and local power dissipation, which limited the endurance of the devices produced. The optimal device must balance low resistance contacts with a more resistive channel, to facilitate phase change switching within the nanowires. These results highlight the importance of contact formation on the switching properties in phase change devices and help guide the future design of more reliable neuromorphic devices.

5.
BMC Infect Dis ; 18(1): 531, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30352556

RESUMO

BACKGROUND: Among men who have sex with men (MSM) in the UK, an estimated 28% have never tested for HIV and only 27% of those at higher risk test at least every 6 months. HIV self-testing (HIVST), where the person takes their own blood/saliva sample and processes it themselves, offers the opportunity to remove many structural and social barriers to testing. Although several randomised controlled trials are assessing the impact of providing HIVST on rates of HIV testing, none are addressing whether this results in increased rates of HIV diagnoses that link to clinical care. Linking to care is the critical outcome because it is the only way to access antiretroviral treatment (ART). We describe here the design of a large, internet-based randomised controlled trial of HIVST, called SELPHI, which aims to inform this key question. METHODS/DESIGN: The SELPHI study, which is ongoing is promoted via social networking website and app advertising, and aims to enroll HIV negative men, trans men and trans women, aged over 16 years, who are living in England and Wales. Apart from the physical delivery of the test kits, all trial processes, including recruitment, take place online. In a two-stage randomisation, participants are first randomised (3:2) to receive a free baseline HIVST or no free baseline HIVST. At 3 months, participants allocated to receive a baseline HIVST (and meeting further eligibility criteria) are subsequently randomised (1:1) to receive the offer of regular (every 3 months) free HIVST, with testing reminders, versus no such offer. The primary outcome from both randomisations is a laboratory-confirmed HIV diagnosis, ascertained via linkage to a national HIV surveillance database. DISCUSSION: SELPHI will provide the first reliable evidence on whether offering free HIVST via the internet increases rates of confirmed HIV diagnoses and linkage to clinical care. The two randomisations reflect the dual objectives of detecting prevalent infections (possibly long-standing) and the more rapid diagnosis of incident HIV infections. It is anticipated that the results of SELPHI will inform future access to HIV self-testing provision in the UK. TRIAL REGISTRATION: DOI 10.1186/ISRCTN20312003 registered 24/10/2016.


Assuntos
Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Adulto , Inglaterra , Feminino , Homossexualidade Masculina , Humanos , Internet , Masculino , Testes Sorológicos , Minorias Sexuais e de Gênero , Rede Social , Inquéritos e Questionários
6.
Proc Natl Acad Sci U S A ; 115(30): E7081-E7090, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29987005

RESUMO

The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington's disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.


Assuntos
Adenina , Adutos de DNA/metabolismo , Dano ao DNA , Doença de Huntington/tratamento farmacológico , Neurônios/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/farmacologia , Adenina Fosforribosiltransferase/genética , Adenina Fosforribosiltransferase/metabolismo , Animais , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , Linhagem Celular Transformada , Adutos de DNA/genética , Modelos Animais de Doenças , Humanos , Doença de Huntington/genética , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Camundongos , Camundongos Transgênicos , Neurônios/patologia , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Transdução de Sinais/genética
7.
Environ Sci Technol ; 51(21): 12302-12309, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29028327

RESUMO

In this work, recovery of aluminum from coagulated primary sludge and its reuse potential as secondary coagulant were investigated. The recovery process consisted of releasing the particle-bound aluminum from primary sludge by acidification (HCl or H2SO4), followed by separation using centrifugation for dissolved coagulant recovery. The recovered coagulant was then reused for treating primary wastewater and overall coagulation efficiency was determined. While with fresh alum, the removal efficiencies of total suspended solids, chemical oxygen demand, total phosphorus, and total nitrogen were 85%, 65%, 80% and 33%, respectively, a drop in removal efficiency of total suspended solids and chemical oxygen demand was observed for recovered aluminum (85-60% and 65-50%, respectively). Nitrogen concentration remained almost constant with each cycle, while phosphorus in the effluent increased by 1 mg/L and 3 mg/L in the first and second cycle, respectively. Precipitation of various aluminum species was modeled for determining the recovery potential of aluminum at low pH. Preliminary cost analysis indicates that optimum recovery of aluminum occurred at a pH of 1.5 for both acids. Struvite precipitation effectively removed increased phosphorus solubilized by acidification at the end of second cycle, however, it also decreased the amount of aluminum available for recycle.


Assuntos
Carbono , Fósforo , Águas Residuárias , Alumínio , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos , Purificação da Água
8.
Am J Crit Care ; 26(4): 303-310, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28668916

RESUMO

BACKGROUND: Family meetings in the intensive care unit are associated with beneficial outcomes for patients, their families, and health care systems, yet these meetings often do not occur in a timely, effective, reliable way. OBJECTIVE: The Department of Veterans Affairs Comprehensive End-of-Life Care Implementation Center sponsored a national initiative to improve family meetings in Veterans Affairs intensive care units across the United States. Process measures of success for the initiative were identified, including development of a curriculum to support facility-based quality improvement projects to implement high-quality family meetings. METHODS: Identified curriculum requirements included suitability for distance learning and applicability to many clinical intensive care units. Curriculum modules were cross-mapped to the "Plan-Do-Study-Act" model to aid in planning quality improvement projects. A questionnaire was e-mailed to users to evaluate the curriculum's effectiveness. RESULTS: Users rated the curriculum's effectiveness in supporting and achieving aims of the initiative as 3.6 on a scale of 0 (not effective) to 4 (very effective). Users adapted the curriculum to meet local needs. The number of users increased from 6 to 17 quality improvement teams in 2 years. All but 3 teams progressed to implementation of an action plan. CONCLUSION: Users were satisfied with the effectiveness and adaptability of a family-meeting quality improvement curriculum to support implementation of a quality improvement project in Veterans Affairs intensive care units. This tool may be useful in facilitating projects to improve the quality of family meetings in other intensive care units.


Assuntos
Comunicação , Currículo , Processos Grupais , Unidades de Terapia Intensiva , Melhoria de Qualidade , Atitude do Pessoal de Saúde , Hospitais Públicos , Humanos , Relações Profissional-Família , Desenvolvimento de Programas/métodos , Melhoria de Qualidade/organização & administração , Inquéritos e Questionários , Estados Unidos , United States Department of Veterans Affairs
9.
Nano Lett ; 16(1): 434-9, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26629610

RESUMO

Thermal management is an important consideration for most nanoelectronic devices, and an understanding of the thermal conductivity of individual device components is critical for the design of thermally efficient systems. However, it can be difficult to directly probe local changes in thermal conductivity within a nanoscale system. Here, we utilize the time-resolved and diffraction-limited imaging capabilities of ultrafast pump-probe microscopy to determine, in a contact-free configuration, the local thermal conductivity in individual Si nanowires (NWs). By suspending single NWs across microfabricated trenches in a quartz substrate, the properties of the same NW both on and off the substrate are directly compared. We find the substrate has no effect on the recombination lifetime or diffusion length of photogenerated charge carriers; however, it significantly impacts the thermal relaxation properties of the NW. In substrate-supported regions, thermal energy deposited into the lattice by the ultrafast laser pulse dissipates within ∼10 ns through thermal diffusion and coupling to the substrate. In suspended regions, the thermal energy persists for over 100 ns, and we directly image the time-resolved spatial motion of the thermal signal. Quantitative analysis of the transient images permits direct determination of the NW's local thermal conductivity, which we find to be a factor of ∼4 smaller than in bulk Si. Our results point to the strong potential of pump-probe microscopy to be used as an all-optical method to quantify the effects of localized environment and morphology on the thermal transport characteristics of individual nanostructured components.

10.
Crit Care Med ; 43(9): 1964-77, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26154929

RESUMO

OBJECTIVES: To describe unique features of neurocritical illness that are relevant to provision of high-quality palliative care; to discuss key prognostic aids and their limitations for neurocritical illnesses; to review challenges and strategies for establishing realistic goals of care for patients in the neuro-ICU; and to describe elements of best practice concerning symptom management, limitation of life support, and organ donation for the neurocritically ill. DATA SOURCES: A search of PubMed and MEDLINE was conducted from inception through January 2015 for all English-language articles using the term "palliative care," "supportive care," "end-of-life care," "withdrawal of life-sustaining therapy," "limitation of life support," "prognosis," or "goals of care" together with "neurocritical care," "neurointensive care," "neurological," "stroke," "subarachnoid hemorrhage," "intracerebral hemorrhage," or "brain injury." DATA EXTRACTION AND SYNTHESIS: We reviewed the existing literature on delivery of palliative care in the neurointensive care unit setting, focusing on challenges and strategies for establishing realistic and appropriate goals of care, symptom management, organ donation, and other considerations related to use and limitation of life-sustaining therapies for neurocritically ill patients. Based on review of these articles and the experiences of our interdisciplinary/interprofessional expert advisory board, this report was prepared to guide critical care staff, palliative care specialists, and others who practice in this setting. CONCLUSIONS: Most neurocritically ill patients and their families face the sudden onset of devastating cognitive and functional changes that challenge clinicians to provide patient-centered palliative care within a complex and often uncertain prognostic environment. Application of palliative care principles concerning symptom relief, goal setting, and family emotional support will provide clinicians a framework to address decision making at a time of crisis that enhances patient/family autonomy and clinician professionalism.


Assuntos
Encefalopatias/terapia , Cuidados Críticos/organização & administração , Unidades de Terapia Intensiva/organização & administração , Cuidados Paliativos/organização & administração , Assistência Terminal/organização & administração , Comunicação , Tomada de Decisões , Indicadores Básicos de Saúde , Humanos , Planejamento de Assistência ao Paciente , Prognóstico , Fatores de Tempo , Obtenção de Tecidos e Órgãos/organização & administração , Suspensão de Tratamento
11.
Chest ; 147(2): 560-569, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25644909

RESUMO

Rapid response teams (RRTs) can effectively foster discussions about appropriate goals of care and address other emergent palliative care needs of patients and families facing life-threatening illness on hospital wards. In this article, The Improving Palliative Care in the ICU (IPAL-ICU) Project brings together interdisciplinary expertise and existing data to address the following: special challenges for providing palliative care in the rapid response setting, knowledge and skills needed by RRTs for delivery of high-quality palliative care, and strategies for improving the integration of palliative care with rapid response critical care. We discuss key components of communication with patients, families, and primary clinicians to develop a goal-directed treatment approach during a rapid response event. We also highlight the need for RRT expertise to initiate symptom relief. Strategies including specific clinician training and system initiatives are then recommended for RRT care improvement. We conclude by suggesting that as evaluation of their impact on other outcomes continues, performance by RRTs in meeting palliative care needs of patients and families should also be measured and improved.


Assuntos
Unidades de Terapia Intensiva/organização & administração , Cuidados Paliativos/organização & administração , Diretivas Antecipadas , Competência Clínica , Comunicação , Enfermagem de Cuidados Críticos , Tomada de Decisões , Equipe de Respostas Rápidas de Hospitais , Humanos , Relações Médico-Paciente
12.
J Proteomics ; 118: 49-62, 2015 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-25449829

RESUMO

UNLABELLED: Although multiple phosphorylation sites are often clustered in substrates, the mechanism of phosphorylation within clusters has not been systematically investigated. Intriguingly, in addition to acidic residues, protein kinase CK2 can use phosphoserine residues as consensus determinants suggesting that CK2 may act in concert with other kinases. We used a peptide array approach to outline optimal consensus sequences for hierarchical phosphorylation by CK2, both in the context of processive, multisite phosphorylation, and in concert with a priming proline-directed kinase. Results suggest that hierarchical phosphorylation involving CK2 requires precise positioning of either multiple phosphodeterminant residues or specific combinations of canonical determinants and phosphodeterminants, and can be as enzymatically favorable as canonical CK2 phosphorylation. Over 1600 human proteins contain at least one CK2 hierarchical consensus motif, and ~20% of these motifs contain at least one reported in vivo phosphorylation site. These motifs occur non-randomly in the human proteome, with significant enrichment in proteins controlling specific cellular processes. Taken together, our results provide strong in vitro evidence that hierarchical phosphorylation may contribute to the regulation of crucial biological processes. In addition, the results suggest a mechanism by which CK2, a constitutively active kinase, can be a regulatory participant in cellular processes. BIOLOGICAL SIGNIFICANCE: Phosphorylation is a crucial regulatory mechanism governing cellular signal transduction pathways, and despite the large number of identified sites to date, most mechanistic studies remain focused on individual phosphorylation sites. This study is the first to systematically determine specific consensus sequences for hierarchical phosphorylation events. The results indicate that individual phosphorylation sites should not be studied in isolation, and that larger, multisite phosphorylation motifs may have profound impact on cellular signaling. This article is part of a Special Issue entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault and Anne-Claude Gingras.


Assuntos
Caseína Quinase II/química , Proteoma/química , Motivos de Aminoácidos , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , Humanos , Fosforilação , Proteoma/genética , Proteoma/metabolismo
13.
Nano Lett ; 14(11): 6287-92, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25259929

RESUMO

Strain-induced changes to the electronic structure of nanoscale materials provide a promising avenue for expanding the optoelectronic functionality of semiconductor nanostructures in device applications. Here we use pump-probe microscopy with femtosecond temporal resolution and submicron spatial resolution to characterize charge-carrier recombination and transport dynamics in silicon nanowires (NWs) locally strained by bending deformation. The electron-hole recombination rate increases with strain for values above a threshold of ∼1% and, in highly strained (∼5%) regions of the NW, increases 6-fold. The changes in recombination rate are independent of NW diameter and reversible upon reduction of the applied strain, indicating the effect originates from alterations to the NW bulk electronic structure rather than introduction of defects. The results highlight the strong relationship between strain, electronic structure, and charge-carrier dynamics in low-dimensional semiconductor systems, and we anticipate the results will assist the development of strain-enabled optoelectronic devices with indirect-bandgap materials such as silicon.

14.
Pediatr Crit Care Med ; 15(8): 762-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25080152

RESUMO

OBJECTIVE: This review highlights benefits that patients, families and clinicians can expect to realize when palliative care is intentionally incorporated into the PICU. DATA SOURCES: We searched the MEDLINE database from inception to January 2014 for English-language articles using the terms "palliative care" or "end of life care" or "supportive care" and "pediatric intensive care." We also hand-searched reference lists and author files and relevant tools on the Center to Advance Palliative Care website. STUDY SELECTION: Two authors (physicians with experience in pediatric intensive care and palliative care) made final selections. DATA EXTRACTION: We critically reviewed the existing data and tools to identify strategies for incorporating palliative care into the PICU. DATA SYNTHESIS: The Improving Palliative Care in the ICU Advisory Board used data and experience to address key questions relating to: pain and symptom management, enhancing quality of life, communication and decision-making, length of stay, sites of care, and grief and bereavement. CONCLUSIONS: Palliative care should begin at the time of a potentially life-limiting diagnosis and continue throughout the disease trajectory, regardless of the expected outcome. Although the PICU is often used for short term postoperative stabilization, PICU clinicians also care for many chronically ill children with complex underlying conditions and others receiving intensive care for prolonged periods. Integrating palliative care delivery into the PICU is rapidly becoming the standard for high quality care of critically ill children. Interdisciplinary ICU staff can take advantage of the growing resources for continuing education in pediatric palliative care principles and interventions.


Assuntos
Comitês Consultivos , Assistência à Saúde/organização & administração , Unidades de Terapia Intensiva Pediátrica/normas , Cuidados Paliativos/normas , Luto , Comunicação , Tomada de Decisões , Humanos , Tempo de Internação , Manejo da Dor , Qualidade de Vida
15.
Nano Lett ; 14(6): 3079-87, 2014 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-24867088

RESUMO

Silicon nanowires incorporating p-type/n-type (p-n) junctions have been introduced as basic building blocks for future nanoscale electronic components. Controlling charge flow through these doped nanostructures is central to their function, yet our understanding of this process is inferred from measurements that average over entire structures or integrate over long times. Here, we have used femtosecond pump-probe microscopy to directly image the dynamics of photogenerated charge carriers in silicon nanowires encoded with p-n junctions along the growth axis. Initially, motion is dictated by carrier-carrier interactions, resulting in diffusive spreading of the neutral electron-hole cloud. Charge separation occurs at longer times as the carrier distribution reaches the edges of the depletion region, leading to a persistent electron population in the n-type region. Time-resolved visualization of the carrier dynamics yields clear, direct information on fundamental drift, diffusion, and recombination processes in these systems, providing a powerful tool for understanding and improving materials for nanotechnology.

16.
Intensive Care Med ; 40(2): 235-48, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24275901

RESUMO

PURPOSE: Pain, dyspnea, and thirst are three of the most prevalent, intense, and distressing symptoms of intensive care unit (ICU) patients. In this report, the interdisciplinary Advisory Board of the Improving Palliative Care in the ICU (IPAL-ICU) Project brings together expertise in both critical care and palliative care along with current information to address challenges in assessment and management. METHODS: We conducted a comprehensive review of literature focusing on intensive care and palliative care research related to palliation of pain, dyspnea, and thirst. RESULTS: Evidence-based methods to assess pain are the enlarged 0-10 Numeric Rating Scale (NRS) for ICU patients able to self-report and the Critical Care Pain Observation Tool or Behavior Pain Scale for patients who cannot report symptoms verbally or non-verbally. The Respiratory Distress Observation Scale is the only known behavioral scale for assessment of dyspnea, and thirst is evaluated by patient self-report using an 0-10 NRS. Opioids remain the mainstay for pain management, and all available intravenous opioids, when titrated to similar pain intensity end points, are equally effective. Dyspnea is treated (with or without invasive or noninvasive mechanical ventilation) by optimizing the underlying etiological condition, patient positioning and, sometimes, supplemental oxygen. Several oral interventions are recommended to alleviate thirst. Systematized improvement efforts addressing symptom management and assessment can be implemented in ICUs. CONCLUSIONS: Relief of symptom distress is a key component of critical care for all ICU patients, regardless of condition or prognosis. Evidence-based approaches for assessment and treatment together with well-designed work systems can help ensure comfort and related favorable outcomes for the critically ill.


Assuntos
Cuidados Críticos/normas , Dispneia/terapia , Manejo da Dor , Cuidados Paliativos , Sede , Dispneia/diagnóstico , Humanos , Unidades de Terapia Intensiva , Medição da Dor , Melhoria de Qualidade
17.
Oncotarget ; 4(4): 560-71, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23599180

RESUMO

Protein kinase CK2 has emerged as a promising candidate for the treatment of a number of cancers. This enzyme is comprised of two catalytic subunits (CK2 and/or CK2α') that form complexes with homodimers of regulatory CK2ß subunits. While catalytic and regulatory CK2 subunits are generally expressed at similar levels to form tetrameric complexes, asymmetric expression of CK2 subunits has been associated with various forms of cancer and the enhanced survival of cancer cells. To elucidate mechanisms responsible for regulation of cancer cell survival by CK2, we recently employed computational and experimental strategies that revealed widespread overlap between sites for CK2 phosphorylation and caspase cleavage. Among candidates with overlapping CK2 and caspase cleavage sites was caspase-3 that is phosphorylated by CK2 to prevent its activation by upstream caspases. To elucidate the precise relationship between CK2 and caspase-3, we modulated expression of individual CK2 subunits and demonstrated that CK2α' exhibits a striking preference for caspase-3 phosphorylation in cells as compared to CK2α and that CK2ß exhibits the capacity to abolish caspase-3 phosphorylation. Since caspase-3 represents the first CK2 substrate selectively phosphorylated by CK2α' in cells, our work highlights divergent functions of the different forms of CK2. Given the involvement of CK2 in a diverse series of biological events and its association with various cancers, this work has important implications for identifying pathological roles of distinct forms of CK2 that could instruct efforts to selectively target individual CK2 subunits for therapy.


Assuntos
Caseína Quinase II/química , Caseína Quinase II/metabolismo , Caspase 3/metabolismo , Neoplasias/metabolismo , Sequência de Aminoácidos , Western Blotting , Caspase 3/química , Domínio Catalítico , Sobrevivência Celular , Células HeLa , Humanos , Imunoprecipitação , Isoenzimas/metabolismo , Dados de Sequência Molecular , Neoplasias/química , Neoplasias/patologia , Fosforilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
18.
Nano Lett ; 13(3): 1336-40, 2013 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-23421654

RESUMO

We have developed a pump-probe microscope capable of exciting a single semiconductor nanostructure in one location and probing it in another with both high spatial and temporal resolution. Experiments performed on Si nanowires enable a direct visualization of the charge cloud produced by photoexcitation at a localized spot as it spreads along the nanowire axis. The time-resolved images show clear evidence of rapid diffusional spreading and recombination of the free carriers, which is consistent with ambipolar diffusion and a surface recombination velocity of ∼10(4) cm/s. The free carrier dynamics are followed by trap carrier migration on slower time scales.

19.
N Engl J Med ; 368(3): 207-17, 2013 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-23323897

RESUMO

BACKGROUND: Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS: We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS: A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P=0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P=0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P=0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log(10) copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS: A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.).


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Progressão da Doença , Esquema de Medicação , Feminino , Seguimentos , HIV/genética , HIV/isolamento & purificação , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Adulto Jovem
20.
J Phys Chem B ; 117(16): 4390-8, 2013 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-23092237

RESUMO

Femtosecond pump-probe microscopy is used to investigate the charge recombination dynamics at different points within a single needle-shaped ZnO rod. Recombination in the tips of the rod occurs through an excitonic or electron-hole plasma state, taking place on a picosecond time scale. Photoexcitation in the larger diameter sections of the interior exhibit dramatically slower recombination that occurs primarily through defects sites, i.e., trap mediated recombination. Transient absorption imaging shows that the spatial variation in the dynamics is also influenced by the cavity resonances supported within the hexagonal cross section of the rod. Finite element simulations suggest that these optical resonator modes produce qualitatively different intensity patterns in the two different locations. Near the end of the rod, the intensity pattern has significant standing-wave character, which leads to the creation of photoexcited carriers in the core of the structure. The larger diameter regions, on the other hand, exhibit intensity distributions in which the whispering gallery (WG) mode character dominates. At these locations, the photoexcited carriers are produced in subsurface depletion zone, where the internal fields separate the electrons and holes and lead to a greater degree of trap recombination on longer time scales.

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