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1.
Cell ; 150(2): 264-78, 2012 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-22817890

RESUMEN

Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is "captured" as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse.


Asunto(s)
Evolución Clonal , Leucemia Mieloide Aguda/genética , Mutación , Adulto , Anciano , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Estudio de Asociación del Genoma Completo , Células Madre Hematopoyéticas/metabolismo , Humanos , Leucemia Mieloide Aguda/fisiopatología , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Recurrencia , Piel/metabolismo , Adulto Joven
2.
Sex Transm Infect ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38897729

RESUMEN

OBJECTIVES: People who use or would benefit from pre-exposure prophylaxis (PrEP) for HIV infection are disproportionately affected by sexually transmitted infections (STIs). Integrating STI services when offering PrEP fosters synergies and efficiencies in response to HIV/STI and promotes people-centred care. Including guidance on STI interventions for people on PrEP may facilitate implementation and uptake. We conducted a global review of national PrEP guidance documents and analysed the inclusion of recommendations for the provision of STI services by country level of income. METHODS: We searched national PrEP guidance documents published by WHO Member States through the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS) databases, the PrEPWatch repository and Google. Information on a range of STI-related interventions was extracted from documents available by October 2023. RESULTS: Of the 113 national PrEP guidance documents retrieved, STIs were mentioned in 77% (90/117). Viral hepatitis B testing and vaccination were recommended by most high-income countries (HICs) and low-income and middle-income countries (LMICs). Recommendation for syphilis testing was prominent in HICs (91%) and moderately noted in LMICs (68%). Gonorrhoea and chlamydia testing was recommended frequently in HICs (88%) and 42% in LMICs. However, the review noted that, to a much lesser extent, specific type of testing for these pathogens was mentioned. Recommendation for quarterly STI testing for syphilis, gonorrhoea and chlamydia was ubiquitous, while the need to offer STI partner services was rarely mentioned. CONCLUSIONS: PrEP services offer an opportunity for improved and expanded STI services, increasing person-centred care and addressing STI epidemics alongside HIV. Our review highlights the strengths and gaps in incorporating critical STI interventions into national PrEP normative guidance. Addressing these gaps through a stepwise approach and increasing targeted testing and partner services can help improve quality of care and support an effective response to HIV and other STIs.

3.
Sex Health ; 212024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833542

RESUMEN

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/métodos , Asia , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Piridonas/administración & dosificación , Dicetopiperazinas
4.
BMC Genomics ; 24(1): 156, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36978008

RESUMEN

BACKGROUND: Understanding how heterogeneous ß-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture. RESULTS: We integrate pancreatic islet single-cell and bulk RNA sequencing data to identify ß-cell subpopulations based on gene expression and characterize genetic networks associated with ß-cell function in obese SM/J mice. We identify ß-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated with normoglycemic-obesity. CONCLUSIONS: By integrating single-cell and bulk islet transcriptomes, our study explores ß-cell heterogeneity and identifies novel subpopulations and genetic pathways associated with ß-cell function in obesity.


Asunto(s)
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ratones , Animales , Transcriptoma , Control Glucémico , Células Secretoras de Insulina/metabolismo , Obesidad/genética , Obesidad/metabolismo , Ácidos Grasos/metabolismo , Insulina/metabolismo , Diabetes Mellitus Tipo 2/genética
5.
AIDS Behav ; 27(11): 3755-3766, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37351685

RESUMEN

Differentiated service delivery and new products, such as long-acting injectable cabotegravir (CAB-LA) and the dapivirine vaginal ring (DVR), could increase uptake and use of pre-exposure prophylaxis (PrEP) for HIV prevention. We explored PrEP provider perspectives on differentiated PrEP service delivery and new PrEP products to inform World Health Organization (WHO) guidelines and programme implementation. 150 PrEP providers who participated in a WHO survey were randomly selected and 67 were invited for interviews based on geographic representation, provider cadre, gender, experience with community-based PrEP service delivery, and familiarity with new PrEP products. Semi-structured interviews were conducted virtually. Key themes were inductively extracted relating to differentiated service delivery and benefits and concerns regarding new PrEP products. 30 PrEP providers from 24 countries were interviewed. Across regions, providers were supportive of differentiated service delivery to respond to clients' needs and preferences, maintain services during COVID-19, and ensure access for priority populations that may face access challenges. Providers welcomed prospects of offering CAB-LA to their clients but had concerns about HIV testing, costs, and the need for clinic-based services, including staff who can administer injections. Providers felt the DVR was potentially important for some cisgender women, especially young clients and female sex workers, and raised fewer concerns compared to injectable PrEP. Providers' views are critical for the development of guidelines and implementing programmes that will best serve PrEP users. Understanding areas where provider capacities and biases may create barriers can define opportunities for training and support to ensure that providers can deliver effective programmes.

7.
Harm Reduct J ; 20(1): 16, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36782321

RESUMEN

BACKGROUND: The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. METHODS: Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. RESULTS: PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. CONCLUSIONS: This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.


Asunto(s)
Fármacos Anti-VIH , Consumidores de Drogas , Infecciones por VIH , Profilaxis Pre-Exposición , Abuso de Sustancias por Vía Intravenosa , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico
8.
Mol Pharm ; 19(2): 532-546, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-34958588

RESUMEN

The present study systematically investigates the effect of annealing conditions and the Kolliphor P 407 content on the physicochemical and structural properties of Compritol (glyceryl behenate) and ternary systems prepared via melt cooling (Kolliphor P 407, Compritol, and a hydrophilic API) representing solid-lipid formulations. The physical properties of Compritol and the ternary systems with varying ratios of Compritol and Kolliphor P 407 were characterized using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS) and infrared (IR) spectroscopy, and hot-stage microscopy (HSM), before and after annealing. The change in the chemical profiles of different Compritol components as a function of annealing was evaluated using 1H NMR spectroscopy. While no change in the polymorphic form of API and Kolliphor P 407 occurred during annealing, a systematic conversion of the α- to ß-form was observed in the case of Compritol. Furthermore, the polymorphic transformation of Compritol was found to be dependent on the Kolliphor P 407 content. As per the Flory-Huggins mixing theory, higher miscibility was observed in the case of monobehenin-Kolliphor P 407, monobehenin-dibehenin, and dibehenin-tribehenin binary mixtures. The miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin was confirmed by 1H NMR analysis. The observed higher miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin is proposed as the trigger for the physical separation from the 1,3-diglyceride and triglycerides during melt solidification of the formulations. The phase separation is postulated as the mechanism underlying the formation of a stable ß-polymorphic form (a native form of 1,3-diglyceride) of Compritol upon annealing. This finding is expected to have an important implication for developing stable solid-lipid-surfactant-based drug formulations.


Asunto(s)
Excipientes , Tensoactivos , Rastreo Diferencial de Calorimetría , Composición de Medicamentos , Excipientes/química , Transición de Fase , Solubilidad , Tensoactivos/química
9.
Sex Health ; 18(1): 1-4, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33663685

RESUMEN

The Asia-Pacific region is home to nearly 6 million people living with HIV. Across the region, key populations - men who have sex with men, transgender women, people who inject drugs, sex workers, prisoners - and their sexual partners make up the majority of those living with HIV. While significant progress has been made in the past 5 years towards UNAIDS's 90-90-90 goals (90% of people with HIV diagnosed, 90% on antiretroviral therapy, 90% virologically suppressed), significant gaps remain. The papers in this Special Issue address important questions: are we on track to end the AIDS epidemic in the Asia-Pacific region? And can countries in this region reach the new UNAIDS targets for 2030?


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Minorías Sexuales y de Género , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Asia/epidemiología , Femenino , Homosexualidad Masculina , Humanos , Masculino , Políticas
10.
Genome Res ; 26(1): 108-18, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26556708

RESUMEN

While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use.


Asunto(s)
Bases de Datos Genéticas , Fusión Génica , Transcriptoma , Neoplasias de la Mama/genética , Línea Celular Tumoral , Femenino , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Reproducibilidad de los Resultados , Análisis de Secuencia de ARN
11.
Am J Community Psychol ; 64(1-2): 59-71, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31355969

RESUMEN

Canada's 2015 Truth and Reconciliation Commission published 94 Calls to Action including direction to post-secondary institutions "to integrate Indigenous knowledge and teaching methods into classrooms" as well as to "build student capacity for intercultural understanding, empathy, and mutual respect." In response, Canadian universities have rushed to "Indigenize" and are now competing to hire Indigenous faculty, from a limited pool of applicants. However, it is missing the true spirit of reconciliation for non-Indigenous faculty to continue with the status quo while assigning the sole responsibility of Indigenizing curriculum to these new hires. How can non-Indigenous psychology professors change their teaching to ensure that all students acquire an appreciation of traditional Indigenous knowledge about holistic health and healing practices, as well as an understanding of Canada's history of racist colonization practices and its intergenerational effects? Community psychologists, particularly those who have established relationships with Indigenous communities, have an important role to play. In this article, I survey the existing literature on Indigenizing and decolonizing psychological curriculum and share ways in which I have integrated Indigenous content into my psychology courses. I also reflect upon the successes, questions, and ongoing challenges that have emerged as I worked in collaboration with first Anisinaabek First Nations and then Mi'kmaw/L'nu First Nations.


Asunto(s)
Competencia Cultural/educación , Indígenas Norteamericanos/educación , Pueblos Indígenas/educación , Psicología/educación , Canadá , Colonialismo , Curriculum , Humanos , Indígenas Norteamericanos/etnología , Indígenas Norteamericanos/psicología , Pueblos Indígenas/psicología , Psicología/métodos
12.
Sex Transm Dis ; 45(3): 199-206, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29420449

RESUMEN

BACKGROUND: Female sex workers in Australia have achieved some of the lowest documented prevalences of human immunodeficiency virus (HIV) and other sexually transmissible infections globally but rates overall are increasing in Australia and warrant closer investigation. METHODS: We constructed a retrospective cohort using repeat testing data extracted from a network of 42 sexual health clinics. Poisson and Cox regression were used to determined trends in incidence and risk factors for HIV, chlamydia, gonorrhoea, and infectious syphilis among female sex workers. RESULTS: From 2009 to 2015, 18,475 women reporting sex work attended a participating service. The overall incidence of urogenital chlamydia was 7.7/100 person years (PY), declining by 38% from 2009 to 2013 before increasing by 43% to 2015 (P < 0.001); anorectal chlamydia incidence was 0.6/100 PY, and pharyngeal was 1.9/100 PY, which increased significantly during the study period (P < 0.001, both). For gonorrhoea, the urogenital incidence was 1.4/100 PY, anorectal incidence was 0.3/100 PY, P < 0.001), and 3.6/100 PY for pharyngeal; urogenital incidence doubled during the study period, anorectal increased fivefold, and pharyngeal more than tripled (P < 0.001, all). Incidence of infectious syphilis was 0.4/100 PY, which remained stable from 2009 to 2015 (P = 0.09). There were seven incident infections of HIV among female sex workers (0.1/100 PY). Inconsistent condom use with private partners, higher number of private partner numbers, recent injecting drug use, younger age, and country of birth variously predicted sexually transmissible infections among female sex workers. CONCLUSIONS: Although infectious syphilis and HIV remain uncommon in female sex workers attending Australian sexual health clinics, the increasing incidence of gonorrhoea across anatomical sites and increasing chlamydia after a period of decline demands enhanced health promotion initiatives.


Asunto(s)
Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/aislamiento & purificación , Gonorrea/epidemiología , Neisseria gonorrhoeae/aislamiento & purificación , Trabajadores Sexuales/estadística & datos numéricos , Australia/epidemiología , Infecciones por Chlamydia/microbiología , Estudios de Cohortes , Consumidores de Drogas , Femenino , Gonorrea/microbiología , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Sexo Seguro , Trabajo Sexual , Parejas Sexuales
13.
Mol Pharm ; 15(5): 1901-1908, 2018 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-29659293

RESUMEN

The current study integrates formation enthalpy and traditional slurry experiments to quickly assess the physical stability of cocrystal drug substance candidates for their potential to support drug development. Cocrystals of an antidiabetic drug (GKA) with nicotinamide (NMA), vanillic acid (VLA), and ethyl vanillin (EVL) were prepared and characterized by powder X-ray diffractometry (PXRD), spectroscopic, and thermal techniques. The formation enthalpies of the cocrystals, and their physical mixtures (GKA + coformer) were measured by the differential scanning calorimetry (DSC) method reported by Zhang et al. [ Cryst. Growth Des. 2012 , 12 ( 8 ), 4090 - 4097 ]. The experimentally measured differences in the relative formation enthalpies obtained by integrating the heat flow of each cocrystal against the respective physical mixture were correlated to the physical stability of the cocrystals in the solid state. The relative formation enthalpies of all of the cocrystals studied suggest that the cocrystals are not physically stable at room temperature versus their physical mixtures. To further address relative stability, the cocrystals were slurried in 30% v/v aqueous ethanol, and it was observed that all of the cocrystals revert to GKA within 48 h at room temperature. The slurry experiments are consistent with the relative instability of the cocrystals with respect to their physical mixtures suggested by the DSC results.

14.
Nature ; 481(7382): 506-10, 2012 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-22237025

RESUMEN

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.


Asunto(s)
Evolución Clonal/genética , Genoma Humano/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Células Clonales/efectos de los fármacos , Células Clonales/metabolismo , Células Clonales/patología , Daño del ADN/efectos de los fármacos , Análisis Mutacional de ADN , Genes Relacionados con las Neoplasias/genética , Genoma Humano/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Mutagénesis/efectos de los fármacos , Mutagénesis/genética , Recurrencia , Reproducibilidad de los Resultados
15.
BMC Public Health ; 18(1): 210, 2018 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-29394918

RESUMEN

BACKGROUND: The New South Wales (NSW) HIV Strategy 2016-2020 aims for the virtual elimination of HIV transmission in NSW, Australia, by 2020. Despite high and increasing levels of HIV testing and treatment since 2012, the annual number of HIV diagnoses in NSW has remained generally unchanged. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV infection among gay and bisexual men (GBM) when taken appropriately. However, there have been no population-level studies that evaluate the impact of rapid PrEP scale-up in high-risk GBM. Expanded PrEP Implementation in Communities in NSW (EPIC-NSW) is a population-level evaluation of the rapid, targeted roll-out of PrEP to high-risk individuals. METHODS: EPIC-NSW, is an open-label, single-arm, multi-centre prospective observational study of PrEP implementation and impact. Over 20 public and private clinics across urban and regional areas in NSW have participated in the rapid roll-out of PrEP, supported by strong community mobilization and PrEP promotion. The study began on 1 March 2016, aiming to enroll at least 3700 HIV negative people at high risk of HIV. This estimate took into consideration criteria for PrEP prescription in people at high risk for acquiring HIV as defined in the NSW PrEP guidelines. Study participants receive once daily co-formulated tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and are followed for up to 24 months. Follow-up includes: testing for HIV at 1 month, HIV and other sexually transmissible infections three-monthly, HCV annually and monitoring of renal function six-monthly. Optional online behavioural surveys are conducted quarterly. The co-primary endpoints are (i) HIV diagnoses and incidence in the cohort and (ii) HIV diagnoses in NSW. DISCUSSION: EPIC-NSW is a population-based PrEP implementation trial which targets the entire estimated population of GBM at high risk for HIV infection in NSW. It will provide a unique opportunity to evaluate the population impact of PrEP on a concentrated HIV epidemic. TRIAL REGISTRATION: https://clinicaltrials.gov/ (identifying number NCT02870790 ; registration date 14 August 2016), pre-results stage.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Bisexualidad , Servicios de Salud Comunitaria/organización & administración , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Profilaxis Pre-Exposición/organización & administración , Adolescente , Adulto , Anciano , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Investigación sobre Servicios de Salud , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Nueva Gales del Sur/epidemiología , Estudios Prospectivos , Proyectos de Investigación , Medición de Riesgo , Adulto Joven
16.
BMC Public Health ; 18(1): 297, 2018 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-29490635

RESUMEN

After publication of the article [1], it has been brought to our attention that one of the members of the EPIC-NSW study group has had their name spelt incorrectly in the acknowledgements. The article mentions "Muhammad Hammoud" when in fact the correct spelling is "Mohamed Hammoud".

17.
Sex Transm Infect ; 93(6): 438-444, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28108701

RESUMEN

OBJECTIVE: Assess willingness to use HIV pre-exposure prophylaxis (PrEP), support for others using it and willingness to have sex with partners using PrEP among Australian gay and bisexual men (GBM). METHODS: National, online cross-sectional surveys of Australian GBM were conducted in 2011, 2013 and 2015. Scales measuring support for and willingness to have sex with men using PrEP were developed in 2015 using factor analysis. Trends and associations with key measures were analysed using multivariate logistic regression. RESULTS: During 2011-2015, 3850 surveys were completed by GBM. Willingness to use PrEP among HIV-negative and untested men did not change between 2011 (28.2%) and 2015 (31.7%, p=0.13). In 2015, willingness to use PrEP was independently associated with younger age, having an HIV-positive regular partner, recent condomless anal intercourse with casual male partners (CAIC), more than 10 male sex partners in the previous 6 months, ever having taken postexposure prophylaxis and having fewer concerns about using PrEP. In 2015, 54.5% of GBM supported other GBM taking PrEP and 39% were willing to have sex with men using PrEP. Support for and willingness to have sex with PrEP users were both associated with being HIV-positive, having a university degree and having two or more male partners in the previous 6 months. Willingness to have sex with men on PrEP was also associated with recent CAIC and using party drugs for sex, but was less likely among men who consistently used or had a positive experience using condoms. DISCUSSION: Interest in and support for using PrEP are concentrated among men who engage in higher risk practices and who know more about living with HIV. This is consistent with the targeting of PrEP in Australia.


Asunto(s)
Bisexualidad/psicología , Infecciones por VIH/prevención & control , Homosexualidad Masculina/psicología , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Profilaxis Pre-Exposición/estadística & datos numéricos , Adulto , Australia/epidemiología , Bisexualidad/estadística & datos numéricos , Condones/estadística & datos numéricos , Estudios Transversales , Escolaridad , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Conducta Sexual/psicología , Parejas Sexuales/psicología
18.
Nature ; 469(7331): 529-33, 2011 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-21270892

RESUMEN

'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.


Asunto(s)
Variación Genética , Genoma/genética , Pongo abelii/genética , Pongo pygmaeus/genética , Animales , Centrómero/genética , Cerebrósidos/metabolismo , Cromosomas , Evolución Molecular , Femenino , Reordenamiento Génico/genética , Especiación Genética , Genética de Población , Humanos , Masculino , Filogenia , Densidad de Población , Dinámica Poblacional , Especificidad de la Especie
19.
N Engl J Med ; 368(22): 2059-74, 2013 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-23634996

RESUMEN

BACKGROUND: Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS: We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS: AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS: We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.).


Asunto(s)
Leucemia Mieloide Aguda/genética , Mutación , Adulto , Islas de CpG , Metilación de ADN , Epigenómica , Femenino , Expresión Génica , Fusión Génica , Genoma Humano , Humanos , Leucemia Mieloide Aguda/clasificación , Masculino , MicroARNs/genética , Persona de Mediana Edad , Nucleofosmina , Análisis de Secuencia de ADN/métodos
20.
AIDS Behav ; 20(7): 1564-71, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26803613

RESUMEN

We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men participated; 1251 participated in 2015. Belief in TasP increased from 2.6 % in 2013 to 13.1 % in 2015 (p < 0.001). The increase was most noticeable among HIV-positive men (from 9.7 % to 46.2 %). Support for early treatment increased from 71.8 % to 75.3 % (p = 0.02). Belief in TasP was associated with being HIV-positive, having a tertiary education, having recent condomless anal intercourse with casual male partners, and ever having taken post-exposure prophylaxis. Support for early HIV treatment was associated with being younger, living in New South Wales and being in paid employment. We recommend continued monitoring of the growing gap in belief about TasP between HIV-positive men and HIV-negative/untested men.


Asunto(s)
Bisexualidad/psicología , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina/psicología , Profilaxis Posexposición , Adulto , Estudios Transversales , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Asunción de Riesgos , Conducta Sexual/estadística & datos numéricos , Parejas Sexuales , Minorías Sexuales y de Género , Sexo Inseguro , Adulto Joven
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