PM20D1 is a quantitative trait locus associated with Alzheimer’s disease
<i>PM20D1</i> is a quantitative trait locus associated with Alzheimer’s disease, Published online: 07 May 2018; doi:10.1038/s41591-018-0013-y
Expression of PM20D1 is regulated by long-range chromatin interactions with an Alzheimer’s disease risk haplotype, and PM20D1 overexpression reduces AD-like pathology and cognitive impairment in a rodent model.
Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial
Carboplatin in <i>BRCA1/2</i>-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial, Published online: 30 April 2018; doi:10.1038/s41591-018-0009-7
The phase 3 TNT Trial in subjects with triple-negative breast cancer supports the superiority of carboplatin over docetaxel in BRCA1/2-mutated tumors and a greater response to taxanes in the nonbasal subtype.
Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia
Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia, Published online: 30 April 2018; doi:10.1038/s41591-018-0010-1
An IL-6/STAT3 signature and memory CD8 T cell subset in preinfusion chimeric antigen receptor–expressing T cells associate with response in patients with high-risk chronic lymphocytic leukemia.
Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes
Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes, Published online: 30 April 2018; doi:10.1038/s41591-018-0016-8
Comprehensive integration of mutational and structural alterations in clinically-annotated DLBCL patient samples provides a novel molecular classification of the disease.
Transcript-indexed ATAC-seq for precision immune profiling
Transcript-indexed ATAC-seq for precision immune profiling, Published online: 23 April 2018; doi:10.1038/s41591-018-0008-8
A new technique enabling single-cell analysis of T cell receptor identity and epigenomic state uncovers heterogeneity in normal and leukemic T cells.
Understanding the tumor immune microenvironment (TIME) for effective therapy
Understanding the tumor immune microenvironment (TIME) for effective therapy, Published online: 23 April 2018; doi:10.1038/s41591-018-0014-x
The tumor immune microenvironment influences tumor progression and response to immunotherapy; its further characterization will improve therapeutic outcome.
Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer
Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer, Published online: 23 April 2018; doi:10.1038/s41591-018-0007-9
Poziotinib is a candidate inhibitor for a subset of EGFR or HER2 mutant non–small cell lung cancers that lack effective therapy.
Clonal CD4+ T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation
Clonal CD4<sup>+</sup> T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation, Published online: 23 April 2018; doi:10.1038/s41591-018-0017-7
A shared gene expression program associated with silencing HIV-1 transcription may be critical for persistence of reactivated latent CD4+ T cells in patients with HIV.
Viktor Orban's re-election to a third consecutive term in Hungary offers a preview for western countries of what the health consequences could be for governments that value populism and economic strength over the health of their people. The controversial populist was swept back into power by a wave of support, with a manifesto that included a crackdown on liberal non-governmental organisations. Orban said before the election that his opponents will face “moral, political, and legal revenge”, in the aftermath.
This week, The Lancet, publishes a Special Report on allegations of sexual harassment and abuse at UNAIDS. The report suggests that UNAIDS has at best marginalised and at worst buried allegations of sexual harassment. Its responses have been unduly weak and unacceptable, and the announcements of remediation are too little too late. Furthermore, internal loyalty to the existing leadership seems to trump integrity in the organisation, and has contributed to a culture devoid of transparency and accountability.
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality in the world today. More than a million British people lived with diagnosed COPD in the UK in 2014–15, or just under 2% of the population. COPD admissions to emergency services in the UK are on the rise, but, access to treatments shown to reduce patients' time spent in hospital is still woefully inadequate.
The term lobbying derives from the public lobbies of the UK Houses of Parliament in London, where concerned citizens have gathered since at least the 16th century to speak with elected officials on the sidelines of legislative debates. In today's parlance, lobbying has evolved to represent a more pernicious and systematic approach to influencing lawmakers, occurring much deeper within the corridors of power.
Doctors have only cared for the world, in various ways; the point, however, is to change it. Imagine you are a distinguished Professor of Medicine, the Rector of one of your country's most garlanded universities. Your students are angry. They have seen fellow students at a nearby university rebel against atrociously poor conditions—overcrowding, incompetent curriculum reforms, and feelings of utter alienation. Tensions are palpable. The air is chilled by the threat of violence. What would you do? Let us not judge.
Sexual harassment and assault investigation at UNAIDS draws attention to an endemic problem. Critics say the UN's internal system is flawed and call for external oversight. John Zarocostas reports.
“The malaria fight is at a crossroads. If we don't seize the moment now, our hard-won gains against the disease will be lost,” says Winnie Mpanju-Shumbusho. “After a decade of progress, malaria cases have increased for the first time, and funding for malaria treatments and prevention has plateaued…especially in Africa which carries more than 90% of the disease burden and progress has stalled over the past few years. We need a new movement to mobilise the political will and resources, as well as citizen action, towards effective malaria control and elimination.” As Board Chair of the RBM Partnership to End Malaria, she is in the forefront of global efforts to mobilise the necessary political will and resources to ensure the fight against malaria is renewed with vigour.
From worryingly low precipitation in California to acute water shortages in Cape Town, climate change is exacerbating natural variations in weather patterns. Problems of water use and security are apparent worldwide and underpin Edward Burtynsky: Water Matters, an exhibition at Arup's offices in London's Fitzrovia. Canadian photographer and film maker Burtynsky has been photographing our environment for over 30 years, documenting the industrially ravaged earth in the process. He turned his attention to water in 2009, releasing the critically acclaimed film Watermark with Jennifer Baichwal in 2013.
The American physician and writer, Danielle Ofri, tells the story of a near fatal mistake that she made at the beginning of the second year of her residency. A patient was brought to the emergency room in a diabetic coma, and although her initial management was fine, Ofri then made an error and “proceeded to nearly kill…[the] patient”. Recognising her predicament, she called for senior assistance. When an explanation was demanded of her performance, Ofri's words dried up. Humiliation set in as she was questioned in front of her intern: “I could almost feel myself dying away on the spot.
Public health physician and champion of women in medicine. She was born in Derry, UK, on Sept 2, 1929, and died with heart disease and dementia in London, UK, on Jan 20, 2018, aged 88 years.
We congratulate the African Surgical Outcomes Study team, led by investigators from low-income and middle-income countries, for quantifying the scale of global inequality in surgical care, and for providing measurable goals for future improvement efforts (April 21, p 1589).1 This work also highlights the poor availability of the detailed information necessary to translate these inequalities into potential solutions.2,3 Continuous surveillance systems or registries could provide such information but are notoriously challenging; disparate paper-based systems, inadequate resources, and overburdened staff are seemingly insurmountable problems.
In their Commission, Irene Agyepong and colleagues (Dec 23, 2017, p 2803)1 provide a comprehensive report on the pathway to healthier lives for all Africans by 2030. As highlighted in the Commission, we have been involved in training family physicians in Africa for the past 20 years within the framework of the Primary Care and Family Medicine Education (Primafamed) network, a South–South cooperation that brings together family medicine, primary care, and public health in more than 20 African countries.