Star formation shut down by multiphase gas outflow in a galaxy at a redshift of 2.45.

Large-scale outflows driven by supermassive black holes are thought to have a fundamental role in suppressing star formation in massive galaxies. However, direct observational evidence for this hypothesis is still lacking, particularly in the young universe where star-formation quenching is remarkably rapid1-3, thus requiring effective removal of gas4 as opposed to slow gas heating5,6. Although outflows of ionized gas are frequently detected in massive distant galaxies7, the amount of ejected mass is too small to be able to suppress star formation8,9. Gas ejection is expected to be more efficient in the neutral and molecular phases10, but at high redshift these have only been observed in starbursts and quasars11,12. Here we report JWST spectroscopy of a massive galaxy experiencing rapid quenching at a redshift of 2.445. We detect a weak outflow of ionized gas and a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to quench the star formation. Neither X-ray nor radio activity is detected; however, the presence of a supermassive black hole is suggested by the properties of the ionized gas emission lines. We thus conclude that supermassive black holes are able to rapidly suppress star formation in massive galaxies by efficiently ejecting neutral gas.

A recently quenched galaxy 700 million years after the Big Bang.

Local and low-redshift (z < 3) galaxies are known to broadly follow a bimodal distribution: actively star-forming galaxies with relatively stable star-formation rates and passive systems. These two populations are connected by galaxies in relatively slow transition. By contrast, theory predicts that star formation was stochastic at early cosmic times and in low-mass systems1-4. These galaxies transitioned rapidly between starburst episodes and phases of suppressed star formation, potentially even causing temporary quiescence-so-called mini-quenching events5,6. However, the regime of star-formation burstiness is observationally highly unconstrained. Directly observing mini-quenched galaxies in the primordial Universe is therefore of utmost importance to constrain models of galaxy formation and transformation7,8. Early quenched galaxies have been identified out to redshift z < 5 (refs. 9-12) and these are all found to be massive (M⋆ > 1010 M⊙) and relatively old. Here we report a (mini-)quenched galaxy at z = 7.3, when the Universe was only 700 Myr old. The JWST/NIRSpec spectrum is very blue (U-V = 0.16 ± 0.03 mag) but exhibits a Balmer break and no nebular emission lines. The galaxy experienced a short starburst followed by rapid quenching; its stellar mass (4-6 × 108 M⊙) falls in a range that is sensitive to various feedback mechanisms, which can result in perhaps only temporary quenching.

Most of the photons that reionized the Universe came from dwarf galaxies.

The identification of sources driving cosmic reionization, a major phase transition from neutral hydrogen to ionized plasma around 600-800 Myr after the Big Bang1-3, has been a matter of debate4. Some models suggest that high ionizing emissivity and escape fractions (fesc) from quasars support their role in driving cosmic reionization5,6. Others propose that the high fesc values from bright galaxies generate sufficient ionizing radiation to drive this process7. Finally, a few studies suggest that the number density of faint galaxies, when combined with a stellar-mass-dependent model of ionizing efficiency and fesc, can effectively dominate cosmic reionization8,9. However, so far, comprehensive spectroscopic studies of low-mass galaxies have not been done because of their extreme faintness. Here we report an analysis of eight ultra-faint galaxies (in a very small field) during the epoch of reionization with absolute magnitudes between MUV ≈ -17 mag and -15 mag (down to 0.005L⋆ (refs. 10,11)). We find that faint galaxies during the first thousand million years of the Universe produce ionizing photons with log[ξion (Hz erg-1)] = 25.80 ± 0.14, a factor of 4 higher than commonly assumed values12. If this field is representative of the large-scale distribution of faint galaxies, the rate of ionizing photons exceeds that needed for reionization, even for escape fractions of the order of 5%.

A high black-hole-to-host mass ratio in a lensed AGN in the early Universe.

Early JWST observations have uncovered a population of red sources that might represent a previously overlooked phase of supermassive black hole growth1-3. One of the most intriguing examples is an extremely red, point-like object that was found to be triply imaged by the strong lensing cluster Abell 2744 (ref. 4). Here we present deep JWST/NIRSpec observations of this object, Abell2744-QSO1. The spectroscopy confirms that the three images are of the same object, and that it is a highly reddened (AV ≃ 3) broad emission line active galactic nucleus at a redshift of zspec = 7.0451 ± 0.0005. From the width of Hß (full width at half-maximum = 2,800 ± 250 km s-1), we derive a black hole mass of M BH = 4 - 1 + 2 × 1 0 7 M ⊙ . We infer a very high ratio of black-hole-to-galaxy mass of at least 3%, an order of magnitude more than that seen in local galaxies5 and possibly as high as 100%. The lack of strong metal lines in the spectrum together with the high bolometric luminosity (Lbol = (1.1 ± 0.3) × 1045 erg s-1) indicate that we are seeing the black hole in a phase of rapid growth, accreting at 30% of the Eddington limit. The rapid growth and high black-hole-to-galaxy mass ratio of Abell2744-QSO1 suggest that it may represent the missing link between black hole seeds6 and one of the first luminous quasars7.

A small and vigorous black hole in the early Universe.

Several theories have been proposed to describe the formation of black hole seeds in the early Universe and to explain the emergence of very massive black holes observed in the first thousand million years after the Big Bang1-3. Models consider different seeding and accretion scenarios4-7, which require the detection and characterization of black holes in the first few hundred million years after the Big Bang to be validated. Here we present an extensive analysis of the JWST-NIRSpec spectrum of GN-z11, an exceptionally luminous galaxy at z = 10.6, revealing the detection of the [NeIV]λ2423 and CII*λ1335 transitions (typical of active galactic nuclei), as well as semi-forbidden nebular lines tracing gas densities higher than 109 cm-3, typical of the broad line region of active galactic nuclei. These spectral features indicate that GN-z11 hosts an accreting black hole. The spectrum also reveals a deep and blueshifted CIVλ1549 absorption trough, tracing an outflow with velocity 800-1,000 km s-1, probably driven by the active galactic nucleus. Assuming local virial relations, we derive a black hole mass of log ( M BH / M ⊙ ) = 6.2 ± 0.3 , accreting at about five times the Eddington rate. These properties are consistent with both heavy seeds scenarios and scenarios considering intermediate and light seeds experiencing episodic super-Eddington phases. Our finding explains the high luminosity of GN-z11 and can also provide an explanation for its exceptionally high nitrogen abundance.

A medical odyssey of a 72-year-old man with Charcot-Marie-Tooth disease type 2 newly diagnosed with biallelic variants in SORD gene causing sorbitol dehydrogenase deficiency.

A 72-year-old man was referred to the Undiagnosed Diseases Network (UDN) because of gradual progressive weakness in both lower extremities for the past 45 years. He was initially diagnosed as having Charcot-Marie-Tooth disease type 2 (CMT2) without a defined molecular genetic cause. Exome sequencing (ES) failed to detect deleterious neuromuscular variants. Very recently, biallelic variants in sorbitol dehydrogenase (SORD) were discovered to be a novel cause of inherited neuropathies including CMT2 or distal hereditary motor neuropathy (dHMN) referred to as Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy (SORDD, OMIM 618912). The most common variant identified was c.757delG; p.A253Qfs*27. Through the Vanderbilt UDN clinical site, this patient was formally diagnosed with SORDD after the identification of homozygosity for the above SORD frameshift through UDN Genome Sequencing (GS). His medical odyssey was solved by GS and detection of extremely high levels of sorbitol. The diagnosis provided him the opportunity to receive potential treatment with an investigational drug in a clinical trial for SORDD. We suggest that similar studies be considered in other individuals thought to possibly have CMT2 or dHMN.

Carbonaceous dust grains seen in the first billion years of cosmic time.

Large dust reservoirs (up to approximately 108 M⊙) have been detected1-3 in galaxies out to redshift z ≃ 8, when the age of the Universe was only about 600 Myr. Generating substantial amounts of dust within such a short timescale has proven challenging for theories of dust formation4,5 and has prompted the revision of the modelling of potential sites of dust production6-8, such as the atmospheres of asymptotic giant branch stars in low-metallicity environments, supernova ejecta and the accelerated growth of grains in the interstellar medium. However, degeneracies between different evolutionary pathways remain when the total dust mass of galaxies is the only available observable. Here we report observations of the 2,175 Å dust attenuation feature, which is well known in the Milky Way and galaxies at z ≲ 3 (refs. 9-11), in the near-infrared spectra of galaxies up to z ≃ 7, corresponding to the first billion years of cosmic time. The relatively short timescale implied for the formation of carbonaceous grains giving rise to this feature12 suggests a rapid production process, possibly in Wolf-Rayet stars or supernova ejecta.

A population of red candidate massive galaxies ~600 Myr after the Big Bang.

Galaxies with stellar masses as high as roughly 1011 solar masses have been identified1-3 out to redshifts z of roughly 6, around 1 billion years after the Big Bang. It has been difficult to find massive galaxies at even earlier times, as the Balmer break region, which is needed for accurate mass estimates, is redshifted to wavelengths beyond 2.5 µm. Here we make use of the 1-5 µm coverage of the James Webb Space Telescope early release observations to search for intrinsically red galaxies in the first roughly 750 million years of cosmic history. In the survey area, we find six candidate massive galaxies (stellar mass more than 1010 solar masses) at 7.4 ≤ z ≤ 9.1, 500-700 Myr after the Big Bang, including one galaxy with a possible stellar mass of roughly 1011 solar masses. If verified with spectroscopy, the stellar mass density in massive galaxies would be much higher than anticipated from previous studies on the basis of rest-frame ultraviolet-selected samples.

Lessons learned: next-generation sequencing applied to undiagnosed genetic diseases.

Rare genetic disorders, when considered together, are relatively common. Despite advancements in genetics and genomics technologies as well as increased understanding of genomic function and dysfunction, many genetic diseases continue to be difficult to diagnose. The goal of this Review is to increase the familiarity of genetic testing strategies for non-genetics providers. As genetic testing is increasingly used in primary care, many subspecialty clinics, and various inpatient settings, it is important that non-genetics providers have a fundamental understanding of the strengths and weaknesses of various genetic testing strategies as well as develop an ability to interpret genetic testing results. We provide background on commonly used genetic testing approaches, give examples of phenotypes in which the various genetic testing approaches are used, describe types of genetic and genomic variations, cover challenges in variant identification, provide examples in which next-generation sequencing (NGS) failed to uncover the variant responsible for a disease, and discuss opportunities for continued improvement in the application of NGS clinically. As genetic testing becomes increasingly a part of all areas of medicine, familiarity with genetic testing approaches and result interpretation is vital to decrease the burden of undiagnosed disease.

Social accountability and health systems' change, beyond the shock of Covid-19: drawing on histories of technical and activist approaches to rethink a shared code of practice.

BACKGROUND: Recognition of the value of "social accountability" to improve health systems performance and to address health inequities, has increased over the last decades, with different schools of thought engaging in robust dialogue. This article explores the tensions between health policy and systems research and practice on the one hand, and health equity-focussed activism on the other, as distinct yet interacting processes that have both been impacted by the shock effects of the Covid-19 pandemic. This extended commentary brings multidisciplinary voices seeking to look back at health systems history and fundamental social-institutional systems' behaviors in order to contextualize these current debates over how best to push social accountability efforts forward. ANALYSIS: There is a documented history of tension between long and short processes of international health cooperation and intervention. Social accountability approaches, as a more recent strategy to improve health systems performance, intersect with this overarching history of negotiation between differently situated actors both global and local on whether to pursue sustained, slow, often community-driven change or to focus on rapid, measurable, often top-down interventions. Covid-19, as a global public health emergency, resulted in calls for urgent action which have unsurprisingly displaced some of the energy and aspiration for systemic transformation processes. A combination of accountability approaches and mechanisms have their own legitimacy in fostering health systems change, demanding collaboration between those that move both fast and slow, top-down and bottom-up. CONCLUSION: We argue that social accountability, much like all efforts to strengthen health systems, is "everybody's business" and that we must understand better the historical processes that have shaped the field of practice over time to move forward. These differences of perspective, knowledge-base and positioning vis-a-vis interventions or longer-term political commitment should not drive a conflict of legitimacy but instead be named, subsequently enabling the development of a shared code of conduct that applies to the breadth of actors involved in social accountability work. If we are concerned about the state of/status of social accountability within the context of "building back better" we must approach collaboration with a willingness to create dialogue across distinct disciplinary, technical and politically-informed ways of working.

Social Support and Linkage to HIV Care Following Routine HIV Testing in a Ugandan Refugee Settlement.

We aimed to identify factors associated with linkage to care for individuals newly diagnosed with HIV in a refugee settlement. This study was conducted from October 2018 through January 2020 in Nakivale Refugee Settlement in Uganda. We conducted a cross-sectional survey among individuals accessing routine HIV testing services. The survey included questions on demographic factors, physical and mental health conditions, social support, and HIV-related stigma. We collected GPS coordinates of the homes of individuals newly diagnosed with HIV. Associations with linkage to care were assessed using bivariate and multivariable analyses. Linkage to care was defined as clinic attendance within 90 days of a positive HIV test, not including the day of testing. Network analysis was used to estimate the travel distance between participants' homes and HIV clinic and to spatially characterize participants living with HIV and their levels of social support. Of 219 participants diagnosed with HIV (out of 5,568 participants screened), 74.4% linked to HIV care. Those who reported higher social support had higher odds of linking to care compared with those who reported lower social support. On spatial analysis, lower levels of social support were most prevalent in Nakivale Refugee Settlement itself, with more robust social support southeast and west of the study area. Social support is a salient correlate of linkage to care for individuals living in refugee settlements and could be the focus of an intervention for improving uptake of HIV care services.

Power analysis in health policy and systems research: a guide to research conceptualisation.

Power is a growing area of study for researchers and practitioners working in the field of health policy and systems research (HPSR). Theoretical development and empirical research on power are crucial for providing deeper, more nuanced understandings of the mechanisms and structures leading to social inequities and health disparities; placing contemporary policy concerns in a wider historical, political and social context; and for contributing to the (re)design or reform of health systems to drive progress towards improved health outcomes. Nonetheless, explicit analyses of power in HPSR remain relatively infrequent, and there are no comprehensive resources that serve as theoretical and methodological starting points. This paper aims to fill this gap by providing a consolidated guide to researchers wishing to consider, design and conduct power analyses of health policies or systems. This practice article presents a synthesis of theoretical and conceptual understandings of power; describes methodologies and approaches for conducting power analyses; discusses how they might be appropriately combined; and throughout reflects on the importance of engaging with positionality through reflexive praxis. Expanding research on power in health policy and systems will generate key insights needed to address underlying drivers of health disparities and strengthen health systems for all.

Historicising global nutrition: critical reflections on contested pasts and reimagined futures.

The COVID-19 pandemic has provoked a range of economic shocks, food systems shocks, public health crises and political upheavals across the globe, prompting a rethink of associated global systems. Prepandemic anticolonial movements that challenged hierarchies of race, space, gender and expert knowledge in global health took on new meaning in the context of the unequal impacts of the SARS-CoV-2 virus as it moved through different kinds of spaces and distinct political contexts. In light of these dynamics, and the desire of many current practitioners in global health to reimagine the future, the need for critical analyses of the recent past have become more urgent. Here we challenge linear understandings of progress in global health-with a focus on the field of nutrition-by returning to consider a previous cycle of dramatic social, political and economic change that prompted serious challenges to the dominance of Western powers and US-based philanthro-capitalists. With a 'global' health and nutrition audience in mind, we put forward considerations on why a better understanding of the continuities and divergences between this past and the present moment are necessary to challenge a status quo that was, and is, highly flawed.

Quenching of star formation from a lack of inflowing gas to galaxies.

Star formation in half of massive galaxies was quenched by the time the Universe was 3 billion years old1. Very low amounts of molecular gas seem to be responsible for this, at least in some cases2-7, although morphological gas stabilization, shock heating or activity associated with accretion onto a central supermassive black hole are invoked in other cases8-11. Recent studies of quenching by gas depletion have been based on upper limits that are insufficiently sensitive to determine this robustly2-7, or stacked emission with its problems of averaging8,9. Here we report 1.3 mm observations of dust emission from 6 strongly lensed galaxies where star formation has been quenched, with magnifications of up to a factor of 30. Four of the six galaxies are undetected in dust emission, with an estimated upper limit on the dust mass of 0.0001 times the stellar mass, and by proxy (assuming a Milky Way molecular gas-to-dust ratio) 0.01 times the stellar mass in molecular gas. This is two orders of magnitude less molecular gas per unit stellar mass than seen in star forming galaxies at similar redshifts12-14. It remains difficult to extrapolate from these small samples, but these observations establish that gas depletion is responsible for a cessation of star formation in some fraction of high-redshift galaxies.

Under-referral of Plain community members for genetic services despite being qualified for genetic evaluation.

Plain community people (Amish and Mennonites) have increased risk of having recessive genetic disorders. This study was designed to assess the rate of referral of Plain people to genetic services at UPMC Children's Hospital of Pittsburgh. Medical records of Plain patients from a 1-year time period were reviewed. Data collected included demographic information, clinical presentation, referral for genetic services, and diagnosis. Of the 303 patients, 102 (33.7%) had a clinical presentation suggestive of a genetic disorder, yet only 32 of those 102 patients (31.4%) had been evaluated by the division of Medical Genetics. These data indicate that less than half of Plain patients with a clinical presentation suggestive of a genetic disorder had been referred to the division of Medical Genetics for a formal evaluation. Now that under-referral of Plain patients has been confirmed, providers can be educated in order to increase referrals for genetic services and facilitate positive healthcare outcomes for the Plain Community.

What Does "Good" Community and Public Engagement Look Like? Developing Relationships With Community Members in Global Health Research.

Community and public engagement (CPE) is increasingly becoming a key component in global health research. The National Institute for Health Research (NIHR) is one of the leading funders in the UK of global health research and requires a robust CPE element in the research it funds, along with CPE monitoring and evaluation. But what does "good" CPE look like? And what factors facilitate or inhibit good CPE? Addressing these questions would help ensure clarity of expectations of award holders, and inform effective monitoring frameworks and the development of guidance. The work reported upon here builds on existing guidance and is a first step in trying to identify the key components of what "good" CPE looks like, which can be used for all approaches to global health research and in a range of different settings and contexts. This article draws on data collected as part of an evaluation of CPE by 53 NIHR-funded award holders to provide insights on CPE practice in global health research. This data was then debated, developed and refined by a group of researchers, CPE specialists and public contributors to explore what "good" CPE looks like, and the barriers and facilitators to good CPE. A key finding was the importance, for some research, of investing in and developing long term relationships with communities, perhaps beyond the life cycle of a project; this was regarded as crucial to the development of trust, addressing power differentials and ensuring the legacy of the research was of benefit to the community.

Modeling pastoralist movement in response to environmental variables and conflict in Somaliland: Combining agent-based modeling and geospatial data.

Pastoralism is widely practiced in arid lands and is the primary means of livelihood for approximately 268 million people across Africa. Environmental, interpersonal, and transactional variables such as vegetation and water availability, conflict, ethnic tensions, and private/public land delineation influence the movements of these populations. The challenges of climate change and conflict are widely felt by nomadic pastoralists in Somalia, where resources are scarce, natural disasters are increasingly common, and protracted conflict has plagued communities for decades. Bereft of real-time data, researchers and programmatic personnel often turn to post hoc analysis to understand the interaction between climate, conflict, and migration, and design programs to address the needs of nomadic pastoralists. By designing an Agent-Based Model to simulate the movement of nomadic pastoralists based on typologically-diverse, historical data of environmental, interpersonal, and transactional variables in Somaliland and Puntland between 2008 and 2018, this study explores how pastoralists respond to changing environments. Through subsequent application of spatial analysis such as choropleth maps, kernel density mapping, and standard deviational ellipses, we characterize the resultant pastoralist population distribution in response to these variables. Outcomes demonstrate a large scale spatio-temporal trend of pastoralists migrating to the southeast of the study area with high density areas in the south of Nugaal, the northwest of Sool, and along the Ethiopian border. While minimal inter-seasonal variability is seen, multiple analyses support the consolidation of pastoralists to specifically favorable regions. Exploration of the large-scale population, climate, and conflict trends allows for cogent narratives and associative hypotheses regarding the pastoralist migration during the study period. While this model produces compelling associations between pastoralist movements and terrestrial and conflict variables, it relies heavily on assumptions and incomplete data that are not necessarily representative of realities on the ground. Given the paucity of data regarding pastoralist decision-making and migration, validation remains challenging.