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.

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 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 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 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.

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.

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.

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.

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.

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.

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.

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.

A massive galaxy in its core formation phase three billion years after the Big Bang.

Most massive galaxies are thought to have formed their dense stellar cores in early cosmic epochs. Previous studies have found galaxies with high gas velocity dispersions or small apparent sizes, but so far no objects have been identified with both the stellar structure and the gas dynamics of a forming core. Here we report a candidate core in the process of formation 11 billion years ago, at redshift z = 2.3. This galaxy, GOODS-N-774, has a stellar mass of 100 billion solar masses, a half-light radius of 1.0 kiloparsecs and a star formation rate of solar masses per year. The star-forming gas has a velocity dispersion of 317 ± 30 kilometres per second. This is similar to the stellar velocity dispersions of the putative descendants of GOODS-N-774, which are compact quiescent galaxies at z ≈ 2 (refs 8-11) and giant elliptical galaxies in the nearby Universe. Galaxies such as GOODS-N-774 seem to be rare; however, from the star formation rate and size of this galaxy we infer that many star-forming cores may be heavily obscured, and could be missed in optical and near-infrared surveys.

Gender-based vulnerability: combining Pareto ranking and spatial statistics to model gender-based vulnerability in Rohingya refugee settlements in Bangladesh.

BACKGROUND: The Rohingya refugee crisis in Bangladesh continues to outstrip humanitarian resources and undermine the health and security of over 900,000 people. Spatial, sector-specific information is required to better understand the needs of vulnerable populations, such as women and girls, and to target interventions with improved efficiency and effectiveness. This study aimed to create a gender-based vulnerability index and explore the geospatial and thematic variations in gender-based vulnerability of Rohingya refugees residing in Bangladesh by utilizing pre-existing, open source data. METHODS: Data sources included remotely-sensed REACH data on humanitarian infrastructure, United Nations Population Fund resource availability data, and the Needs and Population Monitoring Survey conducted by the International Organization for Migration in October 2017. Data gaps were addressed through probabilistic interpolation. A vulnerability index was designed through a process of literature review, variable selection and thematic grouping, normalization, and scorecard creation, and Pareto ranking was employed to rank sites based on vulnerability scoring. Spatial autocorrelation of vulnerability was analyzed with the Global and Anselin Local Moran's I applied to both combined vulnerability index rank and disaggregated thematic ranking. RESULTS: Of the settlements, 24.1% were ranked as 'most vulnerable,' with 30 highly vulnerable clusters identified predominantly in the northwest region of metropolitan Cox's Bazar. Five settlements in Dhokkin, Somitapara, and Pahartoli were categorized as less vulnerable outliers amongst highly vulnerable neighboring sites. Security- and health-related variables appear to be the most significant drivers of gender-specific vulnerability in Cox's Bazar. Clusters of low security and education vulnerability measures are shown near Kutupalong. CONCLUSION: The humanitarian sector produces tremendous amounts of data that can be analyzed with spatial statistics to improve research targeting and programmatic intervention. The critical utilization of these data and the validation of vulnerability indexes are required to improve the international response to the global refugee crisis. This study presents a novel methodology that can be utilized to not only spatially characterize gender-based vulnerability in refugee populations, but can also be calibrated to identify and serve other vulnerable populations during crises.

Point-of-Care Ultrasound Diagnosis of a Catheter-Associated Atrial Thrombus.

BACKGROUND: Emergency physicians can utilize point-of-care thoracic ultrasound to aid in the diagnosis of a variety of cardiovascular and respiratory complaints. CASE REPORT: An emergency physician utilized point-of-care cardiac ultrasound to identify catheter-associated atrial thrombi in a hemodialysis patient presenting with dyspnea. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Based on this case, point-of-care ultrasound can be utilized in patients with central venous catheters, to identify intracardiac thrombi as the cause of dyspnea, thereby facilitating appropriate consultation and treatment.

Improving adolescent sexual and reproductive health in Latin America: reflections from an International Congress.

In February 2014, an international congress on Promoting Adolescent Sexual and Reproductive Health (ASRH) took place in Cuenca, Ecuador. Its objective was to share evidence on effective ASRH intervention projects and programs in Latin America, and to link this evidence to ASRH policy and program development. Over 800 people participated in the three-day event and sixty-six presentations were presented.This paper summarizes the key points of the Congress and of the Community Embedded Reproductive Health Care for Adolescents (CERCA) project. It aims at guiding future ASRH research and policy in Latin America. 1. Context matters. Individual behaviors are strongly influenced by the social context in which they occur, through determinants at the individual, relational, family, community and societal levels. Gender norms/attitudes and ease of communication are two key determinants. 2. Innovative action. There is limited and patchy evidence of effective approaches to reach adolescents with the health interventions they need at scale. Yet, there exist several promising and innovative examples of providing comprehensive sexuality education through conventional approaches and using new media, improving access to health services, and reaching adolescents as well as families and community members using community-based interventions were presented at the Congress. 3. Better measurement. Evaluation designs and indicators chosen to measure the effect and impact of interventions are not always sensitive to subtle and incremental changes. This can create a gap between measured effectiveness and the impact perceived by the targeted populations. Thus, one conclusion is that we need more evidence to better determine the factors impeding progress in ASRH in Latin American, to innovate and respond flexibly to changing social dynamics and cultural practices, and to better measure the impact of existing intervention strategies. Yet, this Congress offered a starting point from which to build a multi-agency and multi-country effort to generate specific evidence on ASRH with the aim of guiding policy and program decision-making. In a region that contains substantial barriers of access to ASRH education and services, and some of the highest adolescent pregnancy rates in the world, the participants agreed that there is no time to lose.

The unintended consequences of sex education: an ethnography of a development intervention in Latin America.

This paper is an ethnography of a four-year, multi-disciplinary adolescent sexual and reproductive health intervention in Bolivia, Nicaragua and Ecuador. An important goal of the intervention--and of the larger global field of adolescent sexual and reproductive health--is to create more open parent-to-teen communication. This paper analyzes the project's efforts to foster such communication and how social actors variously interpreted, responded to, and repurposed the intervention's language and practices. While the intervention emphasized the goal of 'open communication,' its participants more often used the term 'confianza' (trust). This norm was defined in ways that might--or might not--include revealing information about sexual activity. Questioning public health assumptions about parent-teen communication on sex, in and of itself, is key to healthy sexual behavior, the paper explores a pragmatics of communication on sex that includes silence, implied expectations, gendered conflicts, and temporally delayed knowledge.

Community embedded reproductive health interventions for adolescents in Latin America: development and evaluation of a complex multi-centre intervention.

BACKGROUND: Adolescents in Latin America are at high risk for unwanted and unplanned pregnancies, which often result in unsafe abortions or poor maternal health outcomes. Both young men and women in the region face an increased risk of sexually transmitted infections due to inadequate sexual and reproductive health information, services and counselling. To date, many adolescent health programmes have targeted a single determinant of sexual and reproductive health. However, recent evidence suggests that the complexity of sexual and reproductive health issues demands an equally multi-layered and comprehensive approach. METHODS: This article describes the development, implementation and evaluation design of the community-embedded reproductive health care for adolescents (CERCA) study in three Latin American cities: Cochabamba (Bolivia), Cuenca (Ecuador) and Managua (Nicaragua). Project CERCA's research methodology builds on existing methodological frameworks, namely: action research, community based participatory research and intervention-mapping.The interventions in each country address distinct target groups (adolescents, parents, local authorities and health providers) and seek improvement of the following sexual health behaviours: communication about sexuality, sexual and reproductive health information-seeking, access to sexual and reproductive health care and safe sexual relationships.In Managua, we implemented a randomised controlled study, and in Cochabamba and Cuenca we adopted a non-randomised controlled study to evaluate the effectiveness of Project CERCA interventions, in addition to a process evaluation. DISCUSSION: This research will result in a methodological framework that will contribute to the improved design and implementation of future adolescent sexual and reproductive health interventions. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01722084).

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.