Search

The Cryogenic Underground Observatory for Rare Events (CUORE) is a detector array comprised by 988 5  cm×5  cm×5  cm TeO_{2} crystals held below 20 mK, primarily searching for neutrinoless double-beta decay in ^{130}Te. Unprecedented in size among cryogenic calorimetric experiments, CUORE provides a promising setting for the study of exotic throughgoing particles. Using the first tonne year of CUORE's exposure, we perform a search for hypothesized fractionally charged particles (FCPs), which are well-motivated by various standard model extensions and would have suppressed interactions with matter. Across the searched range of charges e/24-e/2 no excess of FCP candidate tracks is observed over background, setting leading limits on the underground FCP flux with charges e/24-e/5 at 90% confidence level. Using the low background environment and segmented geometry of CUORE, we establish the sensitivity of tonne-scale subkelvin detectors to diverse signatures of new physics.

We present the model we developed to reconstruct the CUORE radioactive background based on the analysis of an experimental exposure of 1038.4 kg yr. The data reconstruction relies on a simultaneous Bayesian fit applied to energy spectra over a broad energy range. The high granularity of the CUORE detector, together with the large exposure and extended stable operations, allow for an in-depth exploration of both spatial and time dependence of backgrounds. We achieve high sensitivity to both bulk and surface activities of the materials of the setup, detecting levels as low as 10 nBq kg-1 and 0.1 nBq cm-2, respectively. We compare the contamination levels we extract from the background model with prior radio-assay data, which informs future background risk mitigation strategies. The results of this background model play a crucial role in constructing the background budget for the CUPID experiment as it will exploit the same CUORE infrastructure.

This corrects the article DOI: 10.1103/PhysRevLett.126.171801.

In this contribution we present the achievements of the CUORE experiment so far. It is the first tonne-scale bolometric detector and it is in stable data taking since 2018. We reached to collect about 1800 kg×yr of exposure of which more than 1 ton×year have been analysed. The CUORE detector is meant to search for the neutrinoless double β decay (0νββ) of the 130Te isotope. This is a beyond Standard Model process which could establish the nature of the neutrino to be Dirac or a Majorana particle. It is an alternative mode of the two-neutrinos double β decay, a rare decay which have been precisely measured by CUORE in the 130Te. We found no evidence of the 0νββ and we set a Bayesian lower limit of 2.2 ×1025yr on its half-life. The expertise achieved by CUORE set a milestone for any future bolometric detector, including CUPID, which is the planned next generation experiment searching for 0νββ with scintillating bolometers.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first cryogenic experiment searching for 0 νββ decay that has been able to reach the one-tonne mass scale. The detector, located at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, consists of an array of 988 TeO 2 crystals arranged in a compact cylindrical structure of 19 towers. CUORE began its first physics data run in 2017 at a base temperature of about 10 mK and in April 2021 released its 3 rd result of the search for 0 νββ, corresponding to a tonne-year of TeO 2 exposure. This is the largest amount of data ever acquired with a solid state detector and the most sensitive measurement of 0 νββ decay in 130Te ever conducted. We present the current status of CUORE search for 0 νββ with the updated statistics of one tonne-yr. We finally give an update of the CUORE background model and the measurement of the 130Te 2 νββ decay half-life and decay to excited states of 130Xe , studies performed using an exposure of 300.7 kg yr.

The CUORE experiment is a ton-scale array of TeO 2 cryogenic bolometers located at the underground Laboratori Nazionali del Gran Sasso of Istituto Nazionale di Fisica Nucleare (INFN), in Italy. The CUORE detector consists of 988 crystals operated as source and detector at a base temperature of ∼ 10 mK. Such cryogenic temperature is reached and maintained by means of a custom built cryogen-free dilution cryostat, designed with the aim of minimizing the vibrational noise and the environmental radioactivity. The primary goal of CUORE is the search for neutrinoless double beta decay of 130Te , but thanks to its large target mass and ultra-low background it is suitable for the study of other rare processes as well, such as the neutrinoless double beta decay of 128Te. This tellurium isotope is an attractive candidate for the search of this process, due to its high natural isotopic abundance of 31.75%. The transition energy at (866.7 ± 0.7) keV lies in a highly populated region of the energy spectrum, dominated by the contribution of the two-neutrino double beta decay of 130Te. As the first ton-scale infrastructure operating cryogenic TeO 2 bolometers in stable conditions, CUORE is able to achieve a factor > 10 higher sensitivity to the neutrinoless double beta decay of this isotope with respect to past direct experiments.

The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νββ) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νββ decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νββ decay half-life of T_{1/2}>3.6×10^{24}  yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the most sensitive experiment searching for neutrinoless double-beta decay (0νββ) in 130Te. CUORE uses a cryogenic array of 988 TeO2 calorimeters operated at ∼10 mK with a total mass of 741 kg. To further increase the sensitivity, the detector response must be well understood. Here, we present a non-linear thermal model for the CUORE experiment on a detector-by-detector basis. We have examined both equilibrium and dynamic electro-thermal models of detectors by numerically fitting non-linear differential equations to the detector data of a subset of CUORE channels which are well characterized and representative of all channels. We demonstrate that the hot-electron effect and electric-field dependence of resistance in NTD-Ge thermistors alone are inadequate to describe our detectors' energy-dependent pulse shapes. We introduce an empirical second-order correction factor in the exponential temperature dependence of the thermistor, which produces excellent agreement with energy-dependent pulse shape data up to 6 MeV. We also present a noise analysis using the fitted thermal parameters and show that the intrinsic thermal noise is negligible compared to the observed noise for our detectors.

The Cryogenic Underground Observatory for Rare Events (CUORE) is a large-scale cryogenic experiment searching for neutrinoless double-beta decay (0νββ) in Te130. The CUORE detector is made of natural tellurium, providing the possibility of rare event searches on isotopes other than Te130. In this work we describe a search for neutrinoless positron-emitting electron capture (β+EC) decay in Te120 with a total TeO2 exposure of 355.7 kg yr, corresponding to 0.2405 kg yr of Te120. Albeit 0νββ with two final-state electrons represents the most promising channel, the emission of a positron and two 511-keV γ's make 0νβ+EC decay signature extremely clear. To fully exploit the potential offered by the detector modularity we include events with different topology and perform a simultaneous fit of five selected signal signatures. Using blinded data we extract a median exclusion sensitivity of 3.4×1022 yr at 90% credibility interval (C.I.). After unblinding we find no evidence of 0νβ+EC signal and set a 90% C.I. Bayesian lower limit of 2.9×1022 yr on Te120 half-life. This result improves by an order of magnitude the existing limit from the combined analysis of CUORE-0 and Cuoricino.

The possibility that neutrinos may be their own antiparticles, unique among the known fundamental particles, arises from the symmetric theory of fermions proposed by Ettore Majorana in 19371. Given the profound consequences of such Majorana neutrinos, among which is a potential explanation for the matter-antimatter asymmetry of the universe via leptogenesis2, the Majorana nature of neutrinos commands intense experimental scrutiny globally; one of the primary experimental probes is neutrinoless double beta (0νββ) decay. Here we show results from the search for 0νββ decay of 130Te, using the latest advanced cryogenic calorimeters with the CUORE experiment3. CUORE, operating just 10 millikelvin above absolute zero, has pushed the state of the art on three frontiers: the sheer mass held at such ultralow temperatures, operational longevity, and the low levels of ionizing radiation emanating from the cryogenic infrastructure. We find no evidence for 0νββ decay and set a lower bound of the process half-life as 2.2 × 1025 years at a 90 per cent credibility interval. We discuss potential applications of the advances made with CUORE to other fields such as direct dark matter, neutrino and nuclear physics searches and large-scale quantum computing, which can benefit from sustained operation of large payloads in a low-radioactivity, ultralow-temperature cryogenic environment.

The CUORE experiment is searching for the neutrinoless double β decay of the 130Te using cryogenic calorimeters. The CUORE detector consists of 988 TeO2 crystals packed in 19 towers and placed in a cryogenic facility with a base temperature of 10 mK. Crystals are enriched in the isotope 130Te which is the candidate for the neutrinoless double β decay. It is taking data since 2017 at the Laboratori Nazionali del Gran Sasso in Italy. Such a long operation of a bolometric experiment in stable condition has no precedent: by reaching 1 tonne-year of exposure CUORE set a fundamental milestone for any future experiment using this technology. The CUORE collaboration investigated the neutrinoless double β decay of 130Te exploiting the updated 1 tonne-year of statistics, setting a limit of 2.2 × 1025 yr at the 90% of credibility interval on the half-life, with a median sensitivity of 2.8 × 1025 yr.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment searching for neutrino-less double-beta (0νββ) decay that has been able to reach the one-ton scale. The detector, located at the Laboratori Nazionali del Gran Sasso in Italy, consists of an array of 988 TeO2 crystals arranged in a compact cylindrical structure of 19 towers. Following the completion of the detector construction in August 2016, CUORE began its first physics data run in 2017 at a base temperature of about 10 mK. Following multiple optimization campaigns in 2018, CUORE is currently in stable operating mode. In 2019, CUORE released its second result of the search for 0νββ corresponding to a TeO2 exposure of 372.5 kgyr and a median exclusion sensitivity to a 130Te 0νββ decay half-life of 1.7 1025 yr. We find no evidence for 0νββ decay and set a 90% C.I. Bayesian lower limit of 3.2 1025 yr on the 130Te 0νββ decay half-life. We present the current status of CUORE's search for 0νββ. We give an update of the CUORE background model and the measurement of the 130Te two neutrino double-beta (2νββ) decay half-life. Eventually, we show the preliminary results on half-life limits from the analysis of 130Te 0νββ and 2νββ decay to the first 0+ excited state of 130Xe.

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution – comparable to semiconductor detectors – and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined.

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay (0 νββ) in the isotope 130Te. In this work we present the latest results on two searches for the double beta decay (DBD) of 130Te to the first 02+ excited state of 130Xe : the 0 νββ decay and the Standard Model-allowed two-neutrinos double beta decay (2 νββ). Both searches are based on a 372.5 kg× yr TeO2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as S1/20ν=5.6×1024yr for the 0 νββ decay and S1/22ν=2.1×1024yr for the 2 νββ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at 90 % C.I. on the decay half lives is obtained as: (T1/2)02+0ν>5.9×1024yr for the 0 νββ mode and (T1/2)02+2ν>1.3×1024yr for the 2 νββ mode. These represent the most stringent limits on the DBD of 130Te to excited states and improve by a factor ∼ 5 the previous results on this process.

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay (0 νββ) in the isotope 130Te. In this work we present the latest results on two searches for the double beta decay (DBD) of 130Te to the first 02+ excited state of 130Xe : the 0 νββ decay and the Standard Model-allowed two-neutrinos double beta decay (2 νββ). Both searches are based on a 372.5 kg× yr TeO2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as S1/20ν=5.6×1024yr for the 0 νββ decay and S1/22ν=2.1×1024yr for the 2 νββ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at 90 % C.I. on the decay half lives is obtained as: (T1/2)02+0ν>5.9×1024yr for the 0 νββ mode and (T1/2)02+2ν>1.3×1024yr for the 2 νββ mode. These represent the most stringent limits on the DBD of 130Te to excited states and improve by a factor ∼ 5 the previous results on this process.

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20}  yr. This measurement is the most precise determination of the ^{130}Te 2νββ decay half-life to date.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first cryogenic experiment searching for neutrinoless double-beta (0vßß) decay that has been able to reach the one-ton scale. The detector, located at the Laboratori Nazionali del Gran Sasso in Italy, consists of an array of 988 TeO2 crystals arranged in a compact cylindrical structure of 19 towers. Following the completion of the detector construction in August 2016, CUORE began its first physics data run in 2017 at a base temperature of about 10 mK. Following multiple optimization campaigns in 2018, CUORE is currently in stable operating mode. In 2019, CUORE released its 2nd result of the search for 0vßß with a TeO2 exposure of 372.5 kg·yr and a median exclusion sensitivity to a 130Te 0vßß decay half-life of 1.7 · 1025 yr. We find no evidence for 0vßß decay and set a 90% C.I. (credibility interval) Bayesian lower limit of 3.2 · 1025 yr on the 130Te 0vßß decay half-life. In this work, we present the current status of CUORE's search for 0vßß, as well as review the detector performance. Finally, we give an update of the CUORE background model and the measurement of the 130Te two neutrino double-beta (2vßß) decay half-life.

Despite being the feeblest and lightest of the known particles, the neutrinois one of the most abundant particles in the Universe and has played a criticalrole in its evolution. Within standard cosmological models, most of theneutrinos were produced in the Big Bang and completely decoupled from matterafter the first second. During that short time it is possible that through theprocess of Leptogenesis neutrinos helped to produce the matter/anti-matterasymmetry that sets the stage for all of the structures that we see in theuniverse today. However, these theories generally require the condition thatthe neutrino is a so-called Majorana particle, acting as its own anti-particle.The search for the extremely rare neutrinoless double-beta $(0\nu\beta\beta)$decay is currently the most practical way to address this question. Here wepresent the results of the first tonne-year exposure search for$0\nu\beta\beta$ decay of $^{130}$Te with CUORE. With a median half-lifeexclusion sensitivity of $2.8\times10^{25}$ yr, this is the most sensitivesearch for $0\nu\beta\beta$ decay in $^{130}$Te to date. We find no evidencefor $0\nu\beta\beta$ decay and set a lower bound of $T_{1/2} >2.2\times10^{25}$ yr at a 90% credibility interval. CUORE is the largest,coldest solid-state detector operating below 100mK in the world. Theachievement of 1 tonne-year of exposure demonstrates the long-term reliabilityand potential of cryogenic technology at this scale, with wide rangingapplications to next-generation rare-event searches, dark matter searches, andeven large-scale quantum computing.

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20}  yr. This measurement is the most precise determination of the ^{130}Te 2νββ decay half-life to date.

The CUORE experiment is a large bolometric array searching for the leptonnumber violating neutrino-less double beta decay ($0u\beta\beta$) in theisotope $\mathrm{^{130}Te}$. In this work we present the latest results on twosearches for the double beta decay (DBD) of $\mathrm{^{130}Te}$ to the first$0^{+}_2$ excited state of $\mathrm{^{130}Xe}$: the $0u\beta\beta$ decay andthe Standard Model-allowed two-neutrinos double beta decay ($2u\beta\beta$).Both searches are based on a 372.5 kg$\times$yr TeO$_2$ exposure. Thede-excitation gamma rays emitted by the excited Xe nucleus in the final stateyield a unique signature, which can be searched for with low background bystudying coincident events in two or more bolometers. The closely packedarrangement of the CUORE crystals constitutes a significant advantage in thisregard. The median limit setting sensitivities at 90\% Credible Interval (C.I.)of the given searches were estimated as $\mathrm{S^{0u}_{1/2} = 5.6 \times10^{24} \: \mathrm{yr}}$ for the ${0u\beta\beta}$ decay and$\mathrm{S^{2u}_{1/2} = 2.1 \times 10^{24} \: \mathrm{yr}}$ for the${2u\beta\beta}$ decay. No significant evidence for either of the decay modeswas observed and a Bayesian lower bound at $90\%$ C.I. on the decay half livesis obtained as: $\mathrm{(T_{1/2})^{0u}_{0^+_2} > 5.9 \times 10^{24} \:\mathrm{yr}}$ for the $0u\beta\beta$ mode and$\mathrm{(T_{1/2})^{2u}_{0^+_2} > 1.3 \times 10^{24} \: \mathrm{yr}}$ for the$2u\beta\beta$ mode. These represent the most stringent limits on the DBD of$^{130}$Te to excited states and improve by a factor $\sim5$ the previousresults on this process.

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution – comparable to semiconductor detectors – and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the firstcryogenic experiment searching for neutrinoless double-beta ($0u\beta\beta$)decay that has been able to reach the one-ton scale. The detector, located atthe Laboratori Nazionali del Gran Sasso in Italy, consists of an array of 988TeO$_2$ crystals arranged in a compact cylindrical structure of 19 towers.Following the completion of the detector construction in August 2016, CUOREbegan its first physics data run in 2017 at a base temperature of about 10 mK.Following multiple optimization campaigns in 2018, CUORE is currently in stableoperating mode. In 2019, CUORE released its 2\textsuperscript{nd} result of thesearch for $0u\beta\beta$ with a TeO$_2$ exposure of 372.5 kg$\cdot$yr and amedian exclusion sensitivity to a $^{130}$Te $0u\beta\beta$ decay half-lifeof $1.7\cdot 10^{25}$ yr. We find no evidence for $0u\beta\beta$ decay andset a 90\% C.I. (credibility interval) Bayesian lower limit of $3.2\cdot10^{25}$ yr on the $^{130}$Te $0u\beta\beta$ decay half-life. In this work,we present the current status of CUORE's search for $0u\beta\beta$, as wellas review the detector performance. Finally, we give an update of the CUOREbackground model and the measurement of the $^{130}$Te two neutrino double-beta($2u\beta\beta$) decay half-life.

Objective: To assess national and regional trends and causes‐specific distribution of maternal mortality in India. Design: Nationally representative cross‐sectional surveys. Setting: All of India from 1997 to 2020. Sample: About 10 000 maternal deaths among 4.3 million live births over two decades. Methods: We analysed trends in the maternal mortality ratio (MMR) from 1997 through 2020, estimated absolute maternal deaths and examined the causes of maternal death using nationally representative data sources. We partitioned female deaths (aged 15–49 years) and live birth totals, based on the 2001–2014 Million Death Study to United Nations (UN) demographic totals for the country. Main outcome measures: Maternal mortality burden and distribution of causes. Results: The MMR declined in India by about 70% from 398/100 000 live births (95% CI 378–417) in 1997–98 to 99/100 000 (90–108) in 2020. About 1.30 million (95% CI 1.26–1.35 million) maternal deaths occurred between 1997 and 2020, with about 23 800 (95% CI 21 700–26 000) in 2020, with most occurring in poorer states (63%) and among women aged 20–29 years (58%). The MMRs for Assam (215), Uttar Pradesh/Uttarakhand (192) and Madhya Pradesh/Chhattisgarh (170) were highest, surpassing India's 2016–2018 estimate of 113 (95% CI 103–123). After adjustment for education and other variables, the risks of maternal death were highest in rural and tribal areas of north‐eastern and northern states. The leading causes of maternal death were obstetric haemorrhage (47%; higher in poorer states), pregnancy‐related infection (12%) and hypertensive disorders of pregnancy (7%). Conclusions: India could achieve the UN 2030 MMR goals if the average rate of reduction is maintained. However, without further intervention, the poorer states will not. We estimated that 1.3 million Indian women died from maternal causes over the last two decades. Although maternal mortality rates have fallen by 70% overall, the poorer states lag behind. We estimated that 1.3 million Indian women died from maternal causes over the last two decades. Although maternal mortality rates have fallen by 70% overall, the poorer states lag behind. [ABSTRACT FROM AUTHOR]

BackgroundThe high prevalence of COVID-19 has resulted in 200,000 deaths as of early 2020. The corresponding mortality rate among different countries and times varies. ObjectiveThis study aims to investigate the relationship between the mortality rate and prevalence of COVID-19 within a country. MethodsWe collected data from the Johns Hopkins Coronavirus Resource Center. These data included the daily cumulative death count, recovered count, and confirmed count for each country. This study focused on a total of 36 countries with over 10,000 confirmed COVID-19 cases. Mortality was the main outcome and dependent variable, and it was computed by dividing the number of COVID-19 deaths by the number of confirmed cases. ResultsThe results of our global panel regression analysis showed that there was a highly significant correlation between prevalence and mortality (ρ=0.8304; P

In 2006, Tahyna virus was isolated from Culex spp. mosquitoes collected in Xinjiang, People's Republic of China. In 2007, to determine whether this virus was infecting humans, we tested serum from febrile patients. We found immunoglobulin (Ig) M and IgG against the virus, which suggests human infection in this region. [ABSTRACT FROM AUTHOR]

Rural communities face healthcare challenges. This study assessed a multicomponent intervention to improve hospital visits and anti-osteoporosis medication (AOM) treatment rates. A total of 567 patients were randomized into three groups. Results showed significant improvements in hospital attendance and AOM treatment in intervention groups compared to usual care group., Purpose: Rural communities face limited healthcare access, financial constraints, and transportation barriers leading to health disparities. This study examined interventions that reduced health disparities in increasing the outpatient attendance and treatment rate of anti-osteoporosis medication (AOM), while identifying factors contributing to therapy refusal in rural communities., Methods: A total of 567 patients were randomized at the community level into three groups: multicomponent integrated care (MIC), osteoporosis care only (OC), and usual care (UC). Fracture Risk Assessment Tool and dual-energy X-ray absorptiometry scans were used to evaluate the osteoporosis and osteoporotic fracture risk. High- and moderate-risk patients were advised to pursue further hospital-based assessments and treatment. Both the MIC and OC groups received five interventions to address rural barriers, including specialist access, disease education, overcoming transportation barriers, peer support, and dedicated case managers. However, UC excluded transportation assistance, peer support, and case management. Outcomes measured included outpatient attendance, AOM treatment rates, and factors affecting hospital assessment refusal, analyzed via multivariable logistic modeling., Results: In the MIC group, 73.3% of patients attended the outpatient clinic and 58.6% received AOM. In the OC group, 81% patients attended and 69.3% received AOM. Conversely, in the UC group, only 4.1% attended and received AOM. Significant differences in attendance and AOM rates were found between the MIC and UC groups and between the OC and UC groups (p < .001 for both). Common barriers included beliefs that treatment was unnecessary and lack of hospital access. Risk factors hindering outpatient attendance include male sex, low education, low budget, multiple disabilities, and osteopenia diagnosis., Conclusion: Addressing transportation barriers and implementing dedicated case management are crucial for improving healthcare access among rural patients., Trial Registration: ClinicalTrials.gov NCT05104034., Competing Interests: Declarations. Conflicts of interest: None. The funders/sponsors had no role in study design, data collection, analysis, publication decision, or manuscript preparation., (© 2025. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: To evaluate the relationship between different dosing intervals of antiosteoporosis medications (AOMs) and the subsequent fracture risk among patients with newly initiated AOM therapies., Patients and Methods: In a nationwide population-based cohort study based on Taiwan's National Health Insurance Research Database, osteoporosis patients with 50 years of age or older who newly initiated AOM from January 1, 2008, to December 31, 2018 (n=336,229) were included. We categorized AOMs into short dosing intervals (oral AOMs) or long dosing intervals (parenteral AOMs). The adherence of treatment by medication possession ratio and subsequent fracture after treatment for 3 years were measured., Results: Among patients who initiated parenteral AOMs, the percentage of patients with high adherence (medication possession ratio ≥75%) increased from 33% in 2008 to 69% in 2018. However, among patients who initiated oral AOMs, the percentage of high adherence remained stable (30%) between 2008 and 2018. The use of parenteral AOMs increased from 1% in 2008 to 62% in 2018. At the same time, the percentage of high adherence of those initiated AOMs significantly increased from 34% in 2008 to 61% in 2018. The risk of subsequent fracture decreased significantly between 2008 and 2018 after controlling for all potential confounders (HR, 0.85; 95% CI, 0.81 to 0.89)., Conclusion: AOMs with long dosing intervals not only increased adherence but also associated with the decrease in subsequent fracture risk at a nationwide scale., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Emergence delirium (ED) is a common postoperative cognitive dysfunction in children. ED may cause distress to patients and their families in the early post-anesthesia period and have long-term adverse effects on children. THE PRIMARY PURPOSE: was to verify whether dexmedetomidine can reduce the occurrence of ED in children., Research Type: Systematic review and meta-analysis of RCTs., Data Acquisition: A search was conducted on Web of Science, WHO Trials, Cochrane Library, Clinical Trials.gov, and PubMed for all published studies from inception to 23 Oct. 2022., Eligibility Criteria: Randomized clinical trials that met the following criteria: patients aged 1-18 years, study site in the PACU (Post-anesthesia care unit), incidence of ED as the primary outcome, and prophylactic use of dexmedetomidine defined as injected before admission to the PACU., Results: A total of 7 randomized trials were included (6 studies during eye and neck surgery, 1 during hernia surgery), involving 512 patients (257 (50.1%) with dexmedetomidine, and 250 (49.9%) with control. ED was observed in 17.51% of the patients treated with dexmedetomidine and in 43.14% of those receiving control (risk ratio (RR) = 0.40, 95 % confidence interval [CI] [0.30-0.55], P < 0.00001). Additionally, the prophylactic application of dexmedetomidine also reduced the occurrence of Post-Operating Nausea and Vomiting (RR = 0.24, 95%CI [0.12-0.49], P = 0.0001) and PACU stay time after extubation (mean difference (MD) = -1.57, 95%CI [-3.07 to -0.07], P = 0.04). However, sensitivity analysis of RCTs showed that our effect estimates were not stable (MD = -1.78, 95%CI [-4.18-0.62], P = 0.15)., Conclusion: The prophylactic use of dexmedetomidine was associated with a reduction of ED. However, our findings only apply to eye and neck surgery., Trial Registration: PROSPERO: CRD42022371840., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background Context: Osteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated., Purpose: This study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment., Study Design: Retrospective nationwide cohort study., Patient Sample: A total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures., Outcome Measures: The risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death., Methods: This is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their antiosteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death., Results: A total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16-2.32), 1.74 (95% CI, 1.25-2.42) and 1.53 (95% CI, 1.14-2.06). If osteoporotic fractures were divided into nonvertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54-1.88) for nonpersistent denosumab users, 1.64 (95% CI: 0.96-2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95-2.43) for nonpersistent bisphosphonate users. However, there was a significantly greater risk of nonvertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33-3.11), 1.80 (95% CI, 1.18-2.76) and 1.56 (95% CI, 1.06-2.27) for nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent users. Noteworthy, nonpersistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22-4.38)., Conclusions: In terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or nonpersistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Discontinuation of denosumab without transitioning to another antiresorptive agent results in rapid bone loss and an increased risk of fracture. Previous randomized studies reported inconsistent results regarding the efficacy of zoledronate as sequential therapy., Objective: To investigate the use of sequential therapy with zoledronate to prevent bone loss and decreased bone mineral density (BMD) after denosumab discontinuation in the first year., Design, Setting, and Participants: The Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial was conducted at a referral center and 2 affiliated hospitals in Taiwan. Recruitment was conducted from April 1, 2019, to May 31, 2021, and a 2-year follow-up was planned. The trial included postmenopausal women and men aged 50 years or older who received regular denosumab treatment for at least 2 years and did not have previous exposure to other antiosteoporosis medication or meet other exclusion criteria., Intervention: Participants were assigned via stratified randomization to 1 of 2 groups: group A received continuous denosumab treatment (60 mg twice yearly) as the positive control, whereas group ZOL received 1 dose of zoledronate (5 mg) in the first year., Main Outcomes and Measures: The coprimary outcomes were BMD percentage changes in the lumbar spine (LS-BMD), total hip (TH-BMD), and femoral neck (FN-BMD), respectively. An intention-to-treat analysis was performed., Results: This study included 101 patients (95 women [94.1%]; median age, 72.0 [IQR, 67.0-76.0] years). There were 25 patients in group A (23 women [92.0%]; median age, 74.0 [IQR, 70.0 to 78.0] years) and 76 in group ZOL (72 women [94.7%]; median age, 71.0 [IQR, 65.7 to 76.0] years). In the first year, group ZOL had a significant median decrease in LS-BMD (-0.68% [IQR, -3.22% to 2.75%]) compared with group A (1.30% [IQR, -0.68% to 5.24%]) (P = .03). No significant differences between groups A and ZOL were observed for TH-BMD (median, 1.12% [IQR, -0.06% to 2.25%] vs 0% [-1.47% to 2.15%]) (P = .24) and FN-BMD (median, 0.17% [IQR, -2.29% to 2.90%] vs 0.18% [-2.73% to 3.88%]) (P = .71). We observed a significant difference in the median LS-BMD percentage change for the ZOL subgroup with 3 or more years of denosumab treatment before enrollment (-3.20% [IQR, -7.89% to 0.68%]) compared with group A (1.30% [IQR, -0.68% to 5.24%]) (P = .003)., Conclusions and Relevance: In this randomized trial of sequential therapy after denosumab discontinuation, bone loss was observed in LS-BMD in the first year among patients receiving zoledronate. A longer duration of denosumab treatment was associated with a further decrease in LS-BMD after zoledronate sequential therapy. Further randomized clinical trials and large-scale studies that investigate the strategies of sequential therapy after long-term denosumab treatment are needed., Trial Registration: ClinicalTrials.gov Identifier: NCT03868033.

Purpose: Patients with osteoporosis are at risk of fractures, which can lead to immobility and reduced quality of life. Early diagnosis and treatment are crucial for preventing fractures, but many patients are not diagnosed until after a fracture has occurred. This study aimed to evaluate the performance of 10 osteoporosis screening tools (OSTs) in rural communities of Taiwan. In this prospective study, a total of 567 senior citizens from rural communities underwent bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA) and ten OSTs were administered. Discrimination analysis was performed using the area under the receiver operating characteristic curve (AUROC). Primary outcomes included area under curve (AUC) value, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The DXA examination revealed that 63.0% of females and 22.4% of males had osteoporosis. Among females, Osteoporosis Index of Risk (OSIRIS) and Osteoporosis Self-Assessment Tool for Asians (OSTA) presented the best AUC value with 0.71 (0.66-0.76) and 0.70 (0.66-0.75), respectively. Among males, BWC had the best AUC value of 0.77 (0.67-0.86), followed by OSTA, Simple Calculated Osteoporosis Risk Estimation (SCORE), and OSIRIS. OSTA and OSIRIS showed acceptable performance in both genders. The specificity of Fracture Risk Assessment Tool (FRAX-H), SCORE, National Osteoporosis Foundation Score, OSIRIS, Osteoporosis Risk Assessment Instrument, Age, Bulk, One or Never Estrogen (ABONE), and Body weight criteria increased in both genders after applying the optimum cut-off. Considering it high AUC and simplicity of use, OSTA appeared to be the recommended tool for seniors of both genders among the ten OSTs. This study provides a viable reference for future development of OSTs in Taiwan. Further adjustment according to epidemiological data and risk factors is recommended while applying OSTs to different cohorts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Hip fractures are a significant health concern, especially in the elderly. Hemiarthroplasty has been the preferred treatment for displaced femoral neck fractures. The use of ceramic femoral heads has recently become popular due to their claimed durability. This study aimed to determine long-term outcomes associated with different implant choices in hemiarthroplasty., Methods: The study sample included patients aged 50 years and above, with an index femoral neck fracture admission and hip hemiarthroplasty identified from Taiwan's National Health Insurance (NHI) claims data (2009-2019). To compare two groups of users of different heads, we performed 1:2 matching of the ceramic group versus metal group according to age, gender, index year, and six major comorbidities. Cumulative incidence rates were assessed for revision, post-operative complications, and medical complications. Cause-Specific hazard Cox models were used to estimate the hazard ratios for the two different implants groups., Results: Among 47,158 patients, 2559 out of 2637 who received ceramic head hemiarthroplasty with co-payment, were successfully matched with 5118 receiving metal head prostheses fully covered by the NHI. Over a mean follow-up of 3.12 years, no significant differences were observed in revision rates between the ceramic and metal head groups. The ceramic head group demonstrated significantly lower risks of postoperative complications and medical complications within 90 days than the metal head group., Conclusions: This study found ceramic implant had lower postoperative complications and medical complication rates than metal head implant in hip hemiarthroplasty, but there was no difference in the revision rates between the two heads., Competing Interests: Declaration of competing interest The sponsor of this study had no role in the study design, data extraction, statistical analysis, or manuscript writing. The authors had no other conflict of interests to report., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Alcohol availability is positively associated with alcohol use and harms, but the influence of socioeconomic status (SES) on these associations is not well established. This population-based cross-sectional study examined neighbourhood-level associations between physical alcohol availability (measured as off- and on-premise alcohol outlet density) and 100% alcohol-attributable emergency department (ED) visits by neighbourhood SES in Ontario, Canada from 2017 to 2019 (n = 19,740). A Bayesian spatial modelling approach was used to assess associations and account for spatial autocorrelation, which produced risk ratios (RRs) and 95% credible intervals (95% CrI). Each additional off-premise alcohol outlet in a neighbourhood was associated with a 3% increased risk of alcohol-attributable ED visits in both men (RR = 1.03, 95%CrI: 1.02-1.04) and women (RR = 1.03, 95% CrI: 1.02-1.04). Positive associations were also observed between on-premise alcohol outlet density and alcohol-attributable ED visits, although effect sizes were small. A disproportionately greater association with ED visits was observed with increasing alcohol outlet density in the lowest compared to higher SES neighbourhoods. Reducing physical alcohol availability may be an important policy lever for reducing alcohol harm and alcohol-attributable health inequities., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Mutations in human CILK1 (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point and nonsense mutations that extinguish kinase activity impair primary cilia function, whereas mutations outside the kinase domain are not well understood. Here, we produced a knock-in mouse equivalent to the human CILK1 A615T variant identified in juvenile myoclonic epilepsy (JME). This residue is in the intrinsically disordered C-terminal region of CILK1 separate from the kinase domain. Mouse embryo fibroblasts (MEFs) with either heterozygous or homozygous A612T mutant alleles exhibited a higher ciliation rate, shorter individual cilia, and upregulation of ciliary Hedgehog signaling. Thus, a single A612T mutant allele was sufficient to impair primary cilia and ciliary signaling in MEFs. Gene expression profiles of wild-type versus mutant MEFs revealed profound changes in cilia-related molecular functions and biological processes. The CILK1 A615T mutant protein was not increased to the same level as the wild-type protein when co-expressed with scaffold protein KATNIP (katanin-interacting protein). Our data show that KATNIP regulation of a JME-associated single-residue variant of CILK1 is compromised, and this impairs the maintenance of primary cilia and Hedgehog signaling.

Objective: Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China., Methods: In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5., Results: Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV., Conclusion: G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Precipitation could affect the transmission of diarrheal diseases. The diverse precipitation patterns across different climates might influence the degree of diarrheal risk from precipitation. This study determined the associations between precipitation and diarrheal mortality in tropical, temperate, and arid climate regions., Methods: Daily counts of diarrheal mortality and 28-day cumulative precipitation from 1997 to 2019 were analyzed across 29 locations in eight middle-income countries (Argentina, Brazil, Costa Rica, India, Peru, the Philippines, South Africa, and Thailand). A two-stage approach was employed: the first stage is conditional Poisson regression models for each location, and the second stage is meta-analysis for pooling location-specific coefficients by climate zone., Results: In tropical climates, higher precipitation increases the risk of diarrheal mortality. Under extremely wet conditions (95th percentile of 28-day cumulative precipitation), diarrheal mortality increased by 17.8% (95% confidence interval [CI] = 10.4%, 25.7%) compared with minimum-risk precipitation. For temperate and arid climates, diarrheal mortality increases in both dry and wet conditions. In extremely dry conditions (fifth percentile of 28-day cumulative precipitation), diarrheal mortality risk increases by 3.8% (95% CI = 1.2%, 6.5%) for temperate and 5.5% (95% CI = 1.0%, 10.2%) for arid climates. Similarly, under extremely wet conditions, diarrheal mortality risk increases by 2.5% (95% CI = -0.1%, 5.1%) for temperate and 4.1% (95% CI = 1.1%, 7.3%) for arid climates., Conclusions: Associations between precipitation and diarrheal mortality exhibit variations across different climate zones. It is crucial to consider climate-specific variations when generating global projections of future precipitation-related diarrheal mortality., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I15).

Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels., Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity., Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform., Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program., Competing Interests: PB, SF, LN, XT, NN, HB, AB, KC, GM, MD, TT, FQ, AG, MP, JC, EM, TL, AR No competing interests declared, AS Has received consulting fees from Apeiron Biologics, Cellenkos, Diffusion Pharmaceuticals, and GlaxoSmithKline outside the submitted work, IB Has served as a consultant for BlueDot and the National Hockey League Players' Association outside the submitted work, PJ Reviewing editor, eLife, (© 2024, Brown et al.)