The galaxy UV luminosity function at z ≃ 2-4; new results on faint-end slope and the evolution of luminosity density

We present a new, robust measurement of the evolving rest-frame ultraviolet (UV) galaxy luminosity function (LF) over the key redshift range from z ≃ 2 to z ≃ 4. Our results are based on the high dynamic range provided by combining the Hubble Ultra Deep Field (HUDF), CANDELS/GOODS-South, and UltraVISTA/COSMOS surveys. We utilize the unparalleled multifrequency photometry available in this survey ‘wedding cake’ to compile complete galaxy samples at z ≃ 2, 3, 4 via photometric redshifts (calibrated against the latest spectroscopy) rather than colour–colour selection, and to determine accurate rest-frame UV absolute magnitudes (M1500) from spectral energy distribution (SED) fitting. Our new determinations of the UV LF extend from M1500 ≃ −22 (AB mag) down to M1500 = −14.5, −15.5 and −16 at z ≃ 2, 3 and 4, respectively (thus, reaching ≃ 3–4 mag fainter than previous blank-field studies at z ≃ 2,3). At z ≃ 2, 3, we find a much shallower faint-end slope (α = −1.32 ± 0.03) than reported in some previous studies (α ≃ −1.7), and demonstrate that this new measurement is robust. By z ≃ 4, the faint-end slope has steepened slightly, to α = −1.43 ± 0.04, and we show that these measurements are consistent with the overall evolutionary trend from z = 0 to 8. Finally, we find that while characteristic number density (ϕ*) drops from z ≃ 2 to z ≃ 4, characteristic luminosity (M*) brightens by ≃ 1 mag. This, combined with the new flatter faint-end slopes, has the consequence that UV luminosity density (and hence unobscured star formation density) peaks at z ≃ 2.5–3, when the Universe was ≃ 2.5 Gyr old

Characterising the evolving KK-band luminosity function using the UltraVISTA, CANDELS and HUDF surveys

We present the results of a new study of the K-band galaxy luminosity function (KLF) at redshifts z<3.75, based on a nested combination of the UltraVISTA, CANDELS and HUDF surveys. The large dynamic range in luminosity spanned by this new dataset (3-4 dex over the full redshift range) is sufficient to clearly demonstrate for the first time that the faint-end slope of the KLF at z>0.25 is relatively steep (-1.3<alpha<-1.5 for a single Schechter function), in good agreement with recent theoretical and phenomenological models. Moreover, based on our new dataset we find that a double Schechter function provides a significantly improved description of the KLF at z0.25 the evolution of the KLF is remarkably smooth, with little or no evolution evident at faint (M_K>-20.5) or bright magnitudes (M_K<-24.5). Instead, the KLF is seen to evolve rapidly at intermediate magnitudes, with the number density of galaxies at M_K~-23 dropping by a factor of ~5 over the redshift interval 0.25<z<3.75. Motivated by this, we explore a simple description of the evolving KLF based on a double Schechter function with fixed faint-end slopes (alpha_1=-0.5, alpha_2=-1.5) and a shared characteristic magnitude (M_K*). According to this parameterisation, the normalisation of the component which dominates the faint-end of the KLF remains approximately constant, with phi*_2 decreasing by only a factor of ~2 between z~0 and z~3.25. In contrast, the component which dominates the bright end of the KLF at low redshifts evolves dramatically, becoming essentially negligible by z~3. Finally, we note that within this parameterisation, the observed evolution of M_K* between z~0 and z~3.25 is entirely consistent with M_K* corresponding to a constant stellar mass of M*~5x10^10 Msun at all redshifts.Comment: 18 pages, 10 figures, accepted for publication in MNRA

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Evolution of galaxies and black holes, and the origin of cosmic reionization

In recent years, advances in deep optical, and especially deep near-infrared imaging with the Hubble Space Telescope (HST) and wide-field ground-based telescopes such as VISTA, have revolutionized our understanding of the cosmological evolution of galaxies and supermassive black-holes (as manifest through active galactic nuclei; AGN). In particular, the dynamic range provided by the survey `wedding cake' of available HST+ground-based optical/IR data offers new opportunities to push the meaningful statistical study of galaxy and AGN evolution out to high redshifts. Much recent attention has focused, unsurprisingly, on using these new data to push studies of galaxy formation back to within a billion years of the Big Bang, and exploring the role of young galaxies in driving cosmic hydrogen reionization during the crucial era corresponding to redshifts z ≃ 6-10. However, these data have not been as thoroughly exploited at intermediate redshifts, and have only recently been used to explore black-hole/AGN evolution. In this thesis I utilise the latest deep optical/near-infrared imaging and spectroscopy to explore three key facets of cosmological evolution. First, I present a new, robust measurement of the evolving rest-frame ultraviolet (UV) galaxy luminosity function (LF) over the key redshift range from z ≃ 2 to z ≃ 4. My results are based on the high dynamic range provided by combining the Hubble Ultra Deep Field (HUDF), CANDELS/GOODS-South, and UltraVISTA/COSMOS surveys. I utilise the unparalleled multi-frequency photometry available in this survey `wedding cake' to compile complete galaxy samples at z ≃ 2; 3; 4 via photometric redshifts (calibrated against the latest spectroscopy). This study is important as the peak of star-formation is shown to happen within a redshift range z = 2 - 4 and determining the exact epoch that the galaxies were forming most of their stars depends significantly on the UV luminosity density which requires robust measurements of the galaxy UV luminosity function and its accurate parameterization. My new determinations of the UV LF extend from M1500 ≃ -22 (AB mag) down to M1500 =-14.5, -15.5 and -16 at z ≃2, 3 and 4 respectively (thus reaching ≃ 3-4 magnitudes fainter than previous blank-field studies at z ≃ 2 - 3). At z ≃ 2 - 3 I find a much shallower faint-end slope (α = -1:32 ± 0:03) than the steeper values (α ≃ -1:7) reported in the literature, and show that this new measurement is robust. By z ≃ 4 the faint-end slope has steepened slightly, to α = -1:43 ± 0:04, and I show that these measurements are consistent with the overall evolutionary trend from z = 0 to z = 8. I then calculate the UV luminosity density (and hence unobscured star-formation density) and show that it peaks at z ≃ 2:5 - 3, when the Universe was ≃ 2:5 Gyr old. Second, I have used these data to revisit the possibility that X-ray AGN played a significant role in cosmic hydrogen reionization which is one of the major processes in the formation of the Universe we see today. Hence, it is really important to understand this phenomenon thoroughly by studying the properties of sources capable of ionising photons, such as star-forming galaxies and high redshift AGNs. Although most recent studies have suggested that the emerging population of young star-forming galaxies can bathe the Universe in sufficient high-energy photons to complete reionization by z ≃ 6, some authors have reasserted the potentially important role of high-redshift AGN in the hydrogen reionization process. In an effort to clarify this situation, I reinvestigate a claimed sample of 22 X-ray detected active galactic nuclei (AGN) at redshifts z > 4, which has reignited the debate as to whether young galaxies or AGN reionized the Universe. These sources lie within the GOODS-S/CANDELS field, and I examine both the robustness of the claimed X-ray detections (within the Chandra 4Ms imaging) and perform an independent analysis of the photometric redshifts of the optical/infrared counterparts. I confirm the reality of only 15 of the 22 reported X-ray detections, and moreover find that only 12 of the 22 optical/infrared counterpart galaxies actually lie robustly at z > 4. I recalculate the evolving far-UV (1500Å) luminosity density produced by AGN at high redshift, and find that it declines rapidly from z ≃ 4 to z ≃ 6, in agreement with several other recent studies of the evolving AGN luminosity function. The associated rapid decline in inferred hydrogen-ionizing emissivity contributed by AGN falls an order-of-magnitude short of the level required to maintain hydrogen ionization at z ≃ 6. I conclude that AGNs make a very minor contribution to cosmic hydrogen reionization. Finally, I have utilized the deep optical/near-infrared survey data to explore the prevalence of quenched/passive galaxies at high redshift. Applying a robust method to isolate passive galaxies from star-forming galaxies is the key to improving our understanding of the quenching process. Focusing primarily on the deep HUDF data-set, I have revisited the effectiveness of simple colour-colour (UVJ) selection techniques in isolating robust samples of quenched galaxies, and find that dust plays a more important role in this selection process than has been previously appreciated. Through careful SED fitting I successfully isolate a sample of apparently dust-free quiescent galaxies in the redshift range 0:5 < z < 4:5 but (at least in the HUDF) fail to find any galaxy which has remained truly quiescent for > 1 Gyr. I conclude by focusing on the properties of a refined/robust sample of apparently quenched galaxies at z > 3, and in particular establishing the contribution of quenched galaxies to stellar-mass density at early times. I conclude with a summary of my findings, and a brief discussion of the most promising avenues for future advances with the next generation of facilities, such as the James Webb Space Telescope (JWST)

Familial Hypercholesterolemia (FH) in Iran: Findings from the Four-Year FH Registry

Background. Familial hypercholesterolemia (FH) is a common autosomal dominant disease. Its diagnosis in Iran was uncommon. Iran registry of FH (IRFH) has been started from 2017 from Isfahan. In this study, we report the four-year FH registry. Methods. The Iran FH registry is an ongoing study which is followed by a dynamic cohort. It has been started from 2017. The patients are selected from laboratories due to high cholesterol level and who have history of premature cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) criteria are used for the detection of FH. Cascade screening is performed for detection of first-degree relative of patients. Results. Among the 997 individuals included in this registry, they were 522 (mean age 51.41±12.91 year), 141 (mean age 51.66±8.3 year), and 129 (mean age 41±16.5 year) patients from laboratories, premature cardiovascular disease, and relatives, respectively. In total, 263 patients were diagnosed with probable or definite FH, and others were in the possible group. Low-density lipoprotein cholesterol (LDL) level was 141.42±45.27 mg/dl in the laboratory group and 54.9% of patients were on LLT treatment. In patients with premature cardiovascular disease and FH, the LDL level was 91.93±32.58 and was on LLT treatment. The LDL concentration in the first relative of FH patients was 152.88±70.77 and 45.7% of them are on LLT therapy. Conclusions. Most of FH patients were underdiagnosed and undertreated before their inclusion in the IRFH. Cascade screening helps in the improvement of diagnosis

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FindingsGlobal all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.InterpretationGlobal adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic