Explore the vast range of titles available.

A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago 1 , 2 . The individual—who is known as the ‘Berlin patient’—underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression. An adult infected with HIV-1 who underwent allogeneic haematopoietic stem-cell transplantation for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor achieved full remission of HIV-1 for 18 months after transplantation and 16 months after cessation of antiretroviral therapy.

Background Venous thromboembolism (VTE) is a common complication among hospitalized patients, hence VTE prophylaxis is essential. Low body weight patients are at an increased risk of bleeding however there are no guideline recommendations regarding dose adjustment in this population. We performed a meta-analysis to determine whether dose reduction for VTE prophylaxis in low-body weight patients reduces the risk of bleeding, without compromising its efficacy. Methods We searched electronic databases from inception to October 2024. We did a random-effects meta-analysis using RevMan 5.4. Data were pooled to obtain a risk ratio (RR) with 95% confidence interval (CI). Heterogeneity and publication bias were assessed with statistic and funnel plot, respectively. Risk of bias was assessed using ROBINS-I and certainty of evidence was assessed using GRADE. Results Seven observational studies with 5,575 individuals were included. Pooled analyses revealed no significant difference in risk of total bleeding [RR 0.78, 95% CI 0.48–1.26] and major bleeding [RR 0.62, 95% CI 0.33–1.15] with reduced dose compared to standard dose anticoagulation, however with high heterogeneity (I 2  = 64%). Excluding studies with baseline characteristics increasing risk of bleeding in the reduced dose group, sensitivity analysis showed that dose reduction significantly decreases the risk of total [RR 0.49, 95% CI 0.30–0.82] and major bleeding [RR 0.42, 95% CI 0.22–0.80], with low heterogeneity (I = 0). In terms of efficacy, there is not enough evidence to show that anticoagulation dose reduction increases risk of VTE [RR 0.74, 95% CI 0.32–1.73]. Conclusion Among low body weight patients, dose reduction for VTE prophylaxis may reduce risk of bleeding, especially major bleeding, without compromising its efficacy in preventing VTE, hence it can be considered in this population. Randomized controlled trials are needed to further support this recommendation.

IntroductionAutologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, ‘Multiple Sclerosis International Stem Cell Transplant, MIST’, showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS.Methods and analysisStarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve ‘no evidence of disease activity’ during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs.Ethics and disseminationThe study was approved by the Yorkshire and Humber—Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences.Trial registration numberISRCTN88667898.

Objective of the study: to present the analysis of the collected data referring to the characteristics of affluent sewage of the Serraria Sewage Treatment Station, in Porto Alegre/RS. Methodology / approach: descriptive research with a quantitative approach and centralized in the case study of the biogas exploration generated for the production of electric energy. Originality / relevance: this study focuses on the technical and economic feasibility for generating electricity from biogas effluent for use at the station itself, serving most of the local loads, as well as the energy conversion technology used from of the internal combustion Cycle Otto, with its accessories. Main results: installation, operation and maintenance costs for five years are estimated at around R$ 4.500.000,00. In addition, the return on invested capital occurs, at most, in 4 years and 7 months. Theoretical / methodological contributions: there is a tendency to increase electricity from the network tariffand the flow of inputs in the UASBs, making self-generation even more viable. Currently, biogas is flared and the sludge generated is deposited in landfills, which makes it possible to produce electricity and supply it to the distribution network. Conclusion: sewage treatment plants consisting of an upstream flow anaerobic sludge deposit followed by active sludge aims to treat effluents, that is, to promote the separation of gases, solids and liquids as a form of sustainable treatment and, in addition, to provide sustainable benefits and resources for society.

The accretion and differentiation of the Earth were a complex set of events, shaped by both astrophysical and geochemical processes. The physical accretion of the Earth occurred within a protoplanetary disk of gas and dust, with the final stages of growth determined by gravitational interactions between large planetary embryos and planetesimals. Differentiation of the Earth into a central metallic core and a surrounding rocky mantle occurred early and was the most influential geochemical event in Earth history, effectively establishing the chemical composition of the core and mantle of the Earth. Models seeking to determine the environmental conditions of this core-mantle differentiation encounter difficulties; no single pressure-temperature regime can explain the chemical abundances of the Earth’s mantle. However, multiple stages of core formation at varying pressures, temperatures, and compositional conditions can explain the composition of the Earth’s mantle.Here, I study the effects of various astrophysical Solar System formation scenarios involving multiple stages of core-mantle differentiation on the chemical and isotopic composition of the terrestrial planets. To do this, I conducted numerical models of multi-stage planetary accretion and core-mantle differentiation. This numerical model calculates the evolving core and mantle compositions of growing planets in astrophysical simulations of Solar System formation. The model takes accretion histories from N-body physics simulations and calculates the evolving geochemistry of the mantle and core undergoing many stages of impact-driven melting and subsequent metal-silicate equilibration. Results from fluid dynamics experiments and smoothed particle hydrodynamics modeling determine the quantities of silicate and metal in the target and impactor bodies that melt and equilibrate with one another following a planetary impact. To calculate changes in the chemical and isotopic composition of a forming planet’s mantle and core, the model references high-pressure laboratory data describing the partitioning coefficients of various elements and their dependence on pressure (P), temperature (T), and redox state ( 2) of the equilibrating materials. The model takes a mass balance approach to metal-silicate equilibration, calculating the redox state based on the composition of the accreting materials and tracking the partitioning behavior of major and trace lithophile elements (Mg, Ca, Al, Na, Hf), moderately siderophile elements (Fe, Si, Ni, O, S, C, Co, V, Cr, W, Mo, Nb, Ta) and highly siderophile elements (Pt, Pd, Ru, Ir).Five chapters are presented in this dissertation: Chapter 1 is a literature review of relevant topics in planetary formation and cosmochemistry. In Chapter 2, I use simulations of core-mantle differentiation during Solar System formation to constrain the early history of the Solar System. Many studies of terrestrial planet formation have proposed potential dynamical pathways for terrestrial planet formation within the Solar System. To distinguish between the relative viability of these scenarios, their geochemical implications must be considered. My work shows that if there is a strong enough redox gradient in the protoplanetary disk, many different astrophysical scenarios can appropriately reproduce the Earth. In Chapter 3, I use these same simulations of Solar System formation to understand the qualities of the formation of Earth’s Moon. The properties of the Moon-forming impactor, Theia, are poorly constrained, as a wide range of lunar formation scenarios are likely physically viable. My work uses the composition of the Earth’s mantle and characteristics of Solar System formation scenarios that successfully form the Earth to constrain the mass and composition of Theia. Results show that Theia cannot be both large relative to Proto-Earth and have a mantle FeO abundance greater than that of the present-day bulk silicate Earth. In Chapter 4, I use simulations of multi-stage accretion and differentiation of the Earth to investigate the role of core-mantle differentiation in setting the isotopic composition of the Earth’s mantle. There is significant debate in the literature about the role that metal-silicate equilibration during terrestrial core formation plays in determining the Fe isotopic composition of the Solar System. Using a model of the iron isotopic system during multi-stage core formation, I show that if the Earth experienced multiple stages of core formation, the isotopic fractionation effects of metal-silicate equilibration on Fe will be diluted and returned toward a chondritic baseline composition. Thus, I use computational modeling to contextualize laboratory measurements and further constrain the early history of the Earth. Finally, Chapter 5 summarizes the key findings of this dissertation.

The outbreak of the novel coronavirus (SARS-CoV-2) in Wuhan, China and subsequentglobal pandemic illustrated the need of accurate forecasting and a greater understanding of the underlying dynamics of infectious diseases.In this dissertation, we examine the six most populous towns in the State of Montana through the lens of the classic SIR model. With this, we show that the six towns in question exhibit similar disease dynamics and population behavior within each wave. Furthermore, we conduct analysis on the age demographics of COVID-19 cases and deaths. This analysis corroborates the findings of the SIR model fits, in that the age demographics of cases, deaths, and case fatality rates are remarkably similar across all six towns, lending credence to the hypothesis that the dynamics of infectious diseases are fundamentally the same within rural towns in America.

A range of people make decisions on a daily basis that can ultimately result in noncitizens’ deportation from the United States. These actors responsible for interpreting and implementing immigration law make up the “guts” of the U.S. immigration system. This dissertation focuses on the actors whose discretion is most likely to matter first in deciding whether a given noncitizen gets put on the deportation conveyer belt—local law enforcement officers—and the actors whose discretion matters last of all in deciding whether a noncitizen gets taken off the same conveyor belt—immigration judges (“IJs”). I elaborate on how the organizational, political, and social environment of these actors contributes to heterogeneity in their decisions. Chapter 2 asks if the motivations behind sheriffs’ decisions to participate in immigration enforcement influence the consequences of such participation. I focus on social influence—influence experienced because of participation in public official associations (“POAs”)—as a motivation for sheriffs’ decisions to get involved in immigration enforcement. I find that (1) POA participation shaped the timing and manner in which counties showed interest in immigration enforcement and (2) those counties that were most likely to have had social influence be a factor in their decision to participate in immigration enforcement subsequently became the counties that escalated commitment to immigration enforcement at the highest levels. Chapter 3 asks how a rapid change in social perceptions of a national-origin group triggered by the COVID-19 pandemic influenced immigration judges’ decision-making in U.S. removal proceedings. This study with Emily Ryo produces three key findings that answer this question. First, we find that Chinese respondents experienced a significantly higher removal rate during the early pandemic period. Second, we find that East and Southeast Asian respondents also experienced a significantly higher removal rate during the early pandemic period. Notably we also found that increases in the number of cases involving Chinese respondents increased the removal rate for East and Southeast Asian respondents during the early months of the pandemic. Third, we found the decline in the removal rate in the later pandemic period was more gradual and lagged for East and Southeast Asian than Chinese respondents. Chapter 4 asks whether having received training at an elite law school influences IJs’ response to different external influences. First, looking at the change between the Obama and Trump administrations, I test the effect of shifts in IJ behavior that accompany changes in presidential administration. Second, I test the effect of tendencies toward conformity in decision-making that comes with higher levels of similarity to fellow judges. Third, I test the effect of responses to crisis, which I do with a case study of increased bias toward Chinese nationals at the onset of the COVID-19 pandemic. Findings generally suggest that IJs who graduated from elite law schools show lower levels of sensitivity to external sources of influence.The dissertation’s conclusion highlights contributions of these studies to the understanding of the administration of immigration law and other bodies of research while also identifying commonalities across studies.

A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago.sup.1,2. The individual--who is known as the 'Berlin patient'--underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5[DELTA]32/[DELTA]32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin's lymphoma using cells from a CCR5[DELTA]32/[DELTA]32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5[DELTA]32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression.

Originality / relevance: this study focuses on the technical and economic feasibility for generating electricity from biogas effluent for use at the station itself, serving most of the local loads, as well as the energy conversion technology used from of the internal combustion Cycle Otto, with its accessories. Metodologia / abordagem: pesquisa descritiva com abordagem quantitativa e centralizada no estudo de caso da exploracao de biogas gerada para producao de energia eletrica. Metodologia/enfoque: investigacion descriptiva con enfoque cuantitativo y centralizada en el estudio de caso de la exploracion de biogas generada para la produccion de energia electrica. Contribuciones teoricas / metodologicas: existe una tendencia a aumentar la electricidad de la tarifa de la red y el flujo de insumos en los UASB, haciendo que la autogeneracion sea aun mas viable. Actualmente, el biogas se quema y el lodo generado se deposita en vertederos, lo que permite producir electricidad y suministrarla a la red de distribucion. Palabras clave: Biogas de aguas residuales. Tratamiento de aguas residuales. Viabilidad economica.