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1.
Animal ; 18(6): 101156, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38718708

RESUMO

Gastrointestinal nematodes (GINs) are a significant threat to the sustainability of global sheep production. Periparturient ewes play a key role in GIN epidemiology, with increased GIN faecal egg counts (FECs) in these ewes resulting in heavy pasture contamination that facilitates parasitic gastroenteritis in immunologically naïve lambs later during the grazing period. Traditionally, blanket anthelmintic treatment would suppress GIN egg outputs in these ewes and subsequent pasture contamination. However, farmers are now advised to implement targeted selective treatment (TST) to reduce anthelmintic use and subsequent anthelmintic resistance development, yet, there is currently limited evidence to determine optimal TST strategies in ewes. In this study, the characteristics of 226 ewes on seven Welsh farms were assessed postlambing to identify factors associated with their individual strongyle FECs using negative binomial mixed model analysis. Nemabiome analysis was conducted on 34 ewes across two study farms using the Oxford Nanopore MinIon platform with an aim of identifying factors associated with variations in ewe nemabiome composition within flocks. The best-fitted model of ewe FEC incorporated ewe body condition score, dag score, breed, and an interaction effect between ewe age and litter size as fixed factors. The addition of a mean FEC value for ewes of a specific litter size on each farm further improved model fit and reduced between-farm variance in the model. Nemabiome analysis revealed significant variation in within flock nemabiome diversity on individual farms, with significantly reduced nemabiome diversity recorded in ewes exhibiting dags and in twin-bearing ewes on respective farms, whilst T. circumcincta was present as a significantly higher proportion of the nemabiome in Suffolk ewes and twin bearing ewes (P < 0.05) in respective flocks. Our data demonstrate that commonly recorded ewe characteristics can be exploited to predict individual periparturient ewe FEC and subsequently may be used as a guide for TST strategies on sheep farms once specific TST thresholds are identified to deliver the optimal balance between minimal pasture contamination and maximal GIN refugia. This study is the first to utilise Oxford Nanopore MinIon sequencing to evaluate the nemabiome of sheep, and to molecularly assess the nemabiome of individual ruminants within a flock/herd, with results indicating that significant within flock variations in nemabiome composition which may have implications for TST and flock management strategies.

2.
bioRxiv ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746186

RESUMO

HIV-1 anti-retroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines. Proviral gene expression was correlated to the level of endogenous gene expression under resting but not activated conditions. Notably, latent proviral promoters were 10010,000X less active than in productively infected cells and had little or no measurable impact on neighboring gene expression under resting or activated conditions. Thus, the site of integration has a dominant effect on the transcriptional activity of intact HIV-1 proviruses in the latent reservoir thereby influencing cytopathic effects and proviral immune evasion.

3.
J Phys Condens Matter ; 36(32)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38697198

RESUMO

Almost all phase-change memory materials (PCM) contain chalcogen atoms, and their chemical bonds have been denoted both as 'electron-deficient' [sometimes referred to as 'metavalent'] and 'electron-rich' ['hypervalent', multicentre]. The latter involve lone-pair electrons. We have performed calculations that can discriminate unambiguously between these two classes of bond and have shown that PCM have electron-rich, 3c-4e ('hypervalent') bonds. Plots of charge transferred between (ET) and shared with (ES) neighbouring atoms cannot on their own distinguish between 'metavalent' and 'hypervalent' bonds, both of which involve single-electron bonds. PCM do not exhibit 'metavalent' bonding and are not electron-deficient; the bonding is electron-rich of the 'hypervalent' or multicentre type.

4.
Sci Rep ; 14(1): 11120, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750131

RESUMO

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.


Assuntos
Elétrons , Método de Monte Carlo , Dosagem Radioterapêutica , Humanos , Aceleradores de Partículas/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia/métodos , Radioterapia de Alta Energia/métodos , Radioterapia de Alta Energia/instrumentação
5.
Opt Lett ; 49(7): 1688-1691, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560837

RESUMO

Mode-locked vertical external cavity semiconductor lasers are a unique class of nonlinear dynamical systems driven far from equilibrium. We present a novel, to the best of our knowledge, experimental result, supported by rigorous microscopic simulations, of two coexisting mode-locked V-cavity configurations sourced by a common gain medium and operating as independent channels at angle controlled separated wavelengths. Microscopic simulations support pulses coincident on the common gain chip extracting photons from a nearby pair of coexisting kinetic holes burned in the carrier distributions.

7.
J Virus Erad ; 10(1): 100364, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38559321

RESUMO

While low- and middle-income countries (LMICs), especially in Southern and Eastern Africa, bear the largest burden of the HIV globally, investigators working on the front lines in these regions are leading a limited number of research efforts, particularly related to HIV cure. Conducting HIV cure research in high-burden HIV LIMCs provides an unparalleled opportunity to formulate innovative research strategies, design trials tailored to the local context, evaluate clinical outcomes within key and vulnerable populations, meaningful involvement of stakeholders, and to shape policies in areas where HIV prevention and cure interventions can yield the most significant impact. Further, the high prevalence of infection, with varied HIV strains affecting large diverse populations, creates a unique environment for studies that would not be feasible in any other part of the world. This underscores the critical importance of addressing obstacles to unlock the full potential of research efforts in these regions. In this viewpoint, we identify significant challenges facing early career investigators in LMICs, particularly in Africa, that hinder their full engagement in HIV cure research. Drawing examples from the International AIDS Society's Research-for-Cure Academy, we provide practical recommendations to overcome barriers that include limited access to funding, effective mentors, educational and career development opportunities, coupled with inadequate investment in infrastructure that contribute towards the limited number of investigators from high-burden HIV LIMCs who are spearheading cutting-edge cure research. Addressing these challenges is crucial to empower investigators who possess unique insights and expertise, and who are well positioned to lead HIV cure-related research efforts. We acknowledge and welcome initiatives that promote capacity building and knowledge exchange between early-career investigators in LMICs and their peers and scientific leaders from high-income countries (HICs). Prioritizing investment in global collaboration and partnership will play a pivotal role in empowering the next generation of African scientists and clinicians. To expedite advancements of cure-related strategies that will be effective in high-burden HIV LMICs, we endorse the sustainable expansion of these pivotal initiatives in these regions, to enhance their effectiveness and hasten progress in the pursuit of a global HIV cure.

8.
Eur J Surg Oncol ; : 108352, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38653586

RESUMO

Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer. The identification of 'druggable' genetic aberrations and the development of novel targeted therapies against them is opening up new treatment strategies. Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. As our understanding of the biology underpinning CCA continues to improve it is highly likely that additional targeted therapies will become available in the near future. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.

9.
J Virus Erad ; 10(1): 100367, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601701

RESUMO

Background: With the advent of antiretroviral therapy (ART), most children living with HIV in sub-Saharan Africa (SSA) are growing toward adolescence, with scarcity of evidence on the size of viral reservoirs to enhance paediatric cure research strategies. This study aims to compare HIV-1 proviral DNA levels according to virological response among adolescents living with perinatally acquired HIV-1 (ALPHIV) and identify associated-factors in the Cameroonian context. Methods: In this observational cohort study, HIV-1 RNA viremia and CD4+ T-cell count were assessed through RT-PCR and flow cytometry respectively at three time-points over 18 months of observation. At the third time-point, 80 randomly-selected participants were classified as with viremia (≥50 HIV-1 copies/mL; n = 40) or without viremia (<50 HIV-1 copies/mL; n = 40); immune-competent (≥500 CD4+ T cells/mm3) or immunocompromised (<500 CD4+ T cells/mm3). Among these participants, total HIV-1 DNA load was quantified through droplet digital PCR using Bio-Rad QX200. Results: Of the 80 randomly-selected adolescents, median [IQR] age was 15 (13-17) years, 56.2% were female, duration on ART was 9.3 [5.4-12.2] years. Among the 40 viremic ones (median viremia 7312 [283-71482]) HIV-1 copies/ml, 75.0% (30/40) were in virological failure (≥1000 HIV-1 copies/ml), while median of CD4 T cells were 494 [360-793] cell/mm3 with 48.8% (39/80) immunocompromised. No significant variation in HIV-1 RNA viremia and CD4 T cell count was observed between the three time-points, and 13.7% (11/80) adolescents remained aviremic and immune-competent throughout (stable adolescents). A positive and moderate correlation (r = 0.59; p < 0.001) was found between HIV-1 DNA levels and HIV- 1 RNA viremia. Regarding the CD4 T cell count, a negative and weak correlation (r = -0.28; p = 0.014) was found with HIV-1 DNA loads only among adolescents with viremia. Starting ART within the first year of life, ART for over 9 years and aviremia appear as predictors of low HIV-1 DNA loads. Conclusion: Among ALPHIV, high HIV-1 RNA indicates an elevated viral reservoir size, representing a drawback to cure research. Interestingly, early ART initiation and longer ARTduration lead to sustained viral control and limited HIV-1 reservoir size. As limited size of viral reservoir appears consistent with viral control and immune competence, adolescents with sustained viral control (about 14% of this target population) would be candidates for analytical ART interruptions toward establishing paediatric post-treatment controllers in SSA.

10.
Neurology ; 102(10): e209247, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38684044

RESUMO

BACKGROUND AND OBJECTIVES: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones. METHODS: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI. Participants with a history of overt stroke were excluded. Infarct masks were manually delineated on T2-fluid-attenuated inversion-recovery MRI and registered to the Montreal Neurological Institute 152 brain atlas to generate an infarct heatmap. Border zone regions between anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA) were quantified using the Digital 3D Brain MRI Arterial Territories Atlas, and logistic regression was applied to identify relationships between infarct distribution, demographics, and stroke risk factors. RESULTS: Of 113 participants with SCD (median age 26.1 years, interquartile range [IQR] 21.6-31.4 years, 51% male), 56 (49.6%) had SCIs. Participants had a median of 5.5 infarcts (IQR 3.2-13.8). Analysis of infarct distribution showed that 350 of 644 infarcts (54.3%) were in 4 border zones of CBF and 294 (45.6%) were in non-border zone territories. More than 90% of infarcts were in 3 regions: the non-border zone ACA and MCA territories and the ACA-MCA border zone. Logistic regression showed that older participants have an increased chance of infarcts in the MCA territory (odds ratio [OR] 1.08; 95% CI 1.03-1.13; p = 0.001) and a decreased chance of infarcts in the ACA-MCA border zone (OR 0.94; 95% CI 0.90-0.97; p < 0.001). The presence of at least 1 stroke risk factor did not predict SCI location in any model. DISCUSSION: When compared with children with SCD, in adults with SCD, older age is associated with expanded zones of tissue infarction that stretch beyond the traditional border zones of CBF, with more than 45% of infarcts in non-border zone regions.


Assuntos
Anemia Falciforme , Infarto Cerebral , Imageamento por Ressonância Magnética , Humanos , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/epidemiologia , Masculino , Feminino , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Adulto , Adulto Jovem , Estudos Transversais , Pessoa de Meia-Idade , Adolescente , Fatores de Risco , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Circulação Cerebrovascular/fisiologia
11.
Ann R Coll Surg Engl ; 106(4): 321-328, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38555869

RESUMO

Genomics is a crucial part of managing surgical disease. This review focuses on some of the genomic advances that are available now and looks to the future of their application in surgical practice. Whole-genome sequencing enables unbiased coverage across the entire human genome of approximately three billion base pairs. Newer technologies, such as those that permit long-read sequence analysis, provide additional information in longer phased fragment and base pair epigenomic (methylomic) data. Whole-genome sequencing is currently available in England for cancers in children, teenagers and young adults, central nervous system tumours, sarcoma and haematological malignancies. Circulating tumour DNA (ctDNA), immunotherapy and pharmacogenomics have emerged as groundbreaking approaches in the field of cancer treatment. These are now revolutionising the way oncologists and surgeons approach curative cancer surgery. Cancer vaccines offer an innovative approach to reducing recurrence after surgery by priming the immune system to trigger an immune response. The Cancer Vaccine Launch Pad project facilitates cancer vaccine studies in England. The BNT122-01 trial is recruiting patients with ctDNA-positive high-risk colorectal cancer after surgery to assess the impact of cancer vaccines. The evolving landscape of cancer treatment demands a dynamic and integrated approach from the surgical multidisciplinary team. Immunotherapy, ctDNA, pharmacogenomics, vaccines, mainstreaming and whole-genome sequencing are just some of the innovations that have the potential to redefine the standards of care. The continued exploration of these innovative diagnostics and therapies, the genomic pathway evolution and their application in diverse cancer types highlights the transformative impact of precision medicine in surgery.


Assuntos
Vacinas Anticâncer , DNA Tumoral Circulante , Neoplasias , Cirurgiões , Criança , Humanos , Adolescente , DNA Tumoral Circulante/genética , Genômica
12.
Acad Med ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498305

RESUMO

PURPOSE: The authors describe use of the workplace-based assessment (WBA) coactivity scale according to entrustable professional activities (EPAs) and assessor type to examine how diverse assessors rate medical students using WBAs. METHOD: A WBA data collection system was launched at Oregon Health and Science University to visualize learner competency in various clinical settings to foster EPA assessment. WBA data from January 14 to June 18, 2021, for medical students (all years) were analyzed. The outcome variable was level of supervisor involvement in each EPA, and the independent variable was assessor type. RESULTS: A total of 7,809 WBAs were included. Most fourth-, third-, and second-year students were assessed by residents or fellows (755 [49.5%], 1,686 [48.5%], and 918 [49.9%], respectively) and first-year students by attending physicians (803 [83.0%]; P < .001). Attendings were least likely to use the highest rating of 4 (1 was available just in case; 2,148 [56.7%] vs 2,368 [67.7%] for residents; P < .001). Learners more commonly sought WBAs from attendings for EPA 2 (prioritize differential diagnosis), EPA 5 (document clinical encounter), EPA 6 (provide oral presentation), EPA 7 (form clinical questions and retrieve evidence-based medicine), and EPA 12 (perform general procedures of a physician). Residents and fellows were more likely to assess students on EPA 3 (recommend and interpret diagnostic and screening tests), EPA 4 (enter and discuss orders and prescriptions), EPA 8 (give and receive patient handover for transitions in care), EPA 9 (collaborate as member of interprofessional team), EPA 10 (recognize and manage patient in need of urgent care), and EPA 11 (obtain informed consent). CONCLUSIONS: Learners preferentially sought resident vs attending supervisors for different EPA assessments. Future research should investigate why learners seek different assessors more frequently for various EPAs and if assessor type variability in WBA levels holds true across institutions.

13.
medRxiv ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38496497

RESUMO

Background: The primary barrier to curing HIV infection is the pool of intact HIV proviruses integrated into host cell DNA throughout the bodies of people living with HIV (PLHIV), called the HIV reservoir. Reservoir size is impacted by the duration of HIV infection, delay in starting antiretroviral therapy (ART), and breakthrough viremia during ART. The leading infectious cause of death worldwide for PLHIV is TB, but we don't know how TB impacts the HIV reservoir. Methods: We designed a case-control study to compare HIV provirus-containing CD4 in PLHIV with vs. without a history of active TB disease. Study participants in the pilot and confirmatory cohort were enrolled at GHESKIO Centers in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of PBMC-derived CD4 cells. For a subset, Th1 and Th2 cytokines were assayed in plasma. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring. Results: In the pilot cohort, we found that PLHIV with history of active pulmonary TB (n=20) had higher intact provirus than PLHIV without history of active TB (n=47) (794 vs 117 copies per million CD4, respectively; p<0.0001). In the confirmatory cohort, the quantity of intact provirus was higher in the TB group (n=13) compared with the non-TB group (n=18) (median 102 vs. 0 intact provirus per million CD4, respectively p=0.03). Additionally, we found that the frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of IL1B (p= 0.0025) and IL2 (p=0.0002). Conclusions: This is the first assessment of HIV provirus using IPDA in a clinical cohort from a resource limited setting, and the finding of larger reservoir in PLHIV with history of TB has significant implications for our understanding of TB-HIV coinfection and HIV cure efforts in TB-endemic settings.

14.
J Immunol ; 212(10): 1564-1578, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38551350

RESUMO

HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH.


Assuntos
Antígenos CD57 , Infecções por HIV , HIV-1 , Células Matadoras Naturais , Humanos , Células Matadoras Naturais/imunologia , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/imunologia , Masculino , Feminino , Antígenos CD57/imunologia , Adulto , Pessoa de Meia-Idade , Memória Imunológica/imunologia , Lectinas Tipo C/imunologia , Receptores Imunológicos , Viremia/imunologia , Viremia/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/tratamento farmacológico , Receptores de IgG/imunologia , Estudos Longitudinais , Antirretrovirais/uso terapêutico
15.
Ann Surg Oncol ; 31(6): 4061-4070, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38494565

RESUMO

BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.


Assuntos
Canal Inguinal , Excisão de Linfonodo , Linfedema , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/cirurgia , Melanoma/patologia , Linfedema/etiologia , Excisão de Linfonodo/efeitos adversos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Seguimentos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Canal Inguinal/cirurgia , Canal Inguinal/patologia , Prognóstico , Taxa de Sobrevida , Perna (Membro) , Idoso , Adulto , Complicações Pós-Operatórias/etiologia , Estadiamento de Neoplasias
16.
Phys Rev Lett ; 132(4): 043201, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335328

RESUMO

We have used quantum control to suppress the impact of random atom positions on coherent population transfer within atom pairs, enabling the observation of dipole-dipole driven Rabi oscillations in a Rydberg gas with hundreds of atoms. The method exploits the reduced coupling-strength sensitivity of the off-resonant Rabi frequency, and coherently amplifies the achievable population transfer in analogy to quasi-phase-matching in nonlinear optics. Simulations reproduce the experimental results and demonstrate the potential benefits of the technique to other many-body quantum control applications.

17.
BMC Psychiatry ; 24(1): 122, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355533

RESUMO

BACKGROUND: Clozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. METHODS AND DESIGN: This is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12-24 years old). AIM AND OBJECTIVES: The primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. DISCUSSION: The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis. TRIAL REGISTRATION: ISRCTN Number: 37176025, IRAS Number: 1004947. TRIAL STATUS: In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.


Assuntos
Antipsicóticos , Clozapina , Transtornos Psicóticos , Esquizofrenia , Criança , Humanos , Adolescente , Idoso , Adulto , Adulto Jovem , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Esquizofrenia Resistente ao Tratamento , Esquizofrenia/terapia , Qualidade de Vida , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
20.
BMC Nephrol ; 25(1): 38, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279146

RESUMO

BACKGROUND: Patient reported experience measures are contemporary quality indicators that focus on evaluation of healthcare delivery processes. While surgical arteriovenous fistulas (otherAVF) are preferred for haemodialysis vascular access, fears about surgery and complications often result in refusal/delays. A new technique of endovascular arteriovenous fistula creation (EndoAVF) has been developed and as part of it's ongoing introduction into our unit, the patient perspective was felt critical to its evaluation. The Vascular Access Questionnaire (VAQ) provides a mechanism for identifying and scoring perceptions in this setting. METHOD: Patients who had previously undergone EndoAVF formation were approached to undertake the VAQ as part of a service evaluation of their experience. In addition to the components of the VAQ, data questions relating to the patient's perception of their access were gathered. Results were compared with a matched historical cohort of surgically created fistulas (otherAVF) patients. RESULTS: Patient satisfaction and self-reported ease of use with EndoAVF were high. Overall VAQ scores were similar between the EndoAVF and the surgically created cohort. Functionally, there was no significant difference in perception of their fistula by patients, irrespective of them being created surgically or radiologically. CONCLUSION: Although numbers in this report are small limiting exploration of preserved inherent heterogeneity, we provide a useful initial patient reported experience and perspectives on comparative functional use of radiologically and surgically created AVFs. As real world experience gathers, future larger cohorts with adequate sampling may allow exploration of patient reported experiences and outcome measures.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Procedimentos Endovasculares , Humanos , Diálise Renal , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/cirurgia , Satisfação do Paciente , Resultado do Tratamento , Grau de Desobstrução Vascular , Estudos Retrospectivos
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