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1.
Eur Urol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38714379

RESUMO

BACKGROUND AND OBJECTIVE: Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. METHODS: For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. PATIENT SUMMARY: The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance.

2.
Br J Cancer ; 130(10): 1593-1598, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615107

RESUMO

Here, we report on the process of a highly impactful and successful creative, collaborative, and multi-partner public engagement project, Radiation Reveal. It brought together ten young adults aged 17-25-year-olds with experience of radiotherapy with researchers at Cancer Research UK RadNet City of London across three 2-hour online workshops. Our aims were to 1) initiate discussions between young adults and radiation researchers, and 2) identify what people wish they had known about radiotherapy before or during treatment. These aims were surpassed; other benefits included peer support, participants' continued involvement in subsequent engagement projects, lasting friendships, creation of support groups for others, and creation and national dissemination of top ten tips for medical professionals and social media resources. A key learning was that this project required a dedicated and (com)passionate person with connections to national cancer charities. When designing the project, constant feedback is also needed from charities and young adults with and without radiotherapy experience. Finally, visually capturing discussions and keeping the door open beyond workshops further enhanced impact. Here, we hope to inform and inspire people to help project the patient voice in all we do.


Assuntos
Neoplasias , Humanos , Adulto Jovem , Adulto , Adolescente , Feminino , Masculino , Neoplasias/radioterapia , Pesquisa Biomédica
3.
Eur Urol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38614820

RESUMO

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.

4.
Chem Sci ; 15(14): 5143-5151, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577363

RESUMO

Data-driven chemistry has garnered much interest concurrent with improvements in hardware and the development of new machine learning models. However, obtaining sufficiently large, accurate datasets of a desired chemical outcome for data-driven chemistry remains a challenge. The community has made significant efforts to democratize and curate available information for more facile machine learning applications, but the limiting factor is usually the laborious nature of generating large-scale data. Transfer learning has been noted in certain applications to alleviate some of the data burden, but this protocol is typically carried out on a case-by-case basis, with the transfer learning task expertly chosen to fit the finetuning. Herein, I develop a machine learning framework capable of accurate chemistry-relevant prediction amid general sources of low data. First, a chemical "foundational model" is trained using a dataset of ∼1 million experimental organic crystal structures. A task specific module is then stacked atop this foundational model and subjected to finetuning. This approach achieves state-of-the-art performance on a diverse set of tasks: toxicity prediction, yield prediction, and odor prediction.

5.
Eur Urol Open Sci ; 63: 81-88, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38572301

RESUMO

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

6.
Eur Urol Open Sci ; 62: 1-7, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38585208

RESUMO

Background and objective: The ability of health care professionals to communicate with patients compassionately and effectively is crucial for shared decision-making, but little research has investigated patient-clinician communication. As part of PIONEER-an international Big Data Consortium led by the European Association of Urology to answer key questions for men with prostate cancer (PCa), funded through the IMI2 Joint Undertaking under grant agreement 777492- we investigated communication between men diagnosed with PCa and the health care professional(s) treating them across Europe. Methods: We used the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Communication 26, which was shared via the PIONEER and patient organisations on March 11, 2022. We sought men who spoke French, Italian, Spanish, German, Dutch, or English who were diagnosed with PCa and were undergoing or had already received treatment for their PCa. Results and limitations: A total of 372 men reported that they communicated with their clinician during either the diagnostic or the treatment period. Overall, the majority of participants reported positive experiences. However, important opportunities to enhance communication were identified, particularly with regard to correcting misunderstandings, understanding the patient's preferred approach to information presentation, addressing challenging questions, supporting the patient's comprehension of information, attending to the patient's emotional needs, and assessing what information had already been given to patients about their disease and treatment, and how much of it was understood. Conclusions and clinical implications: These results help us to identify gaps and barriers to shared treatment decision making. This knowledge will help devise measures to improve patient-health care professional communication in the PCa setting. Patient summary: As part of the PIONEER initiative, we investigated the communication between men diagnosed with prostate cancer and their health care professionals across Europe. A total of 372 men from six different countries participated in the study. Most participants reported positive experiences, but areas where communication could be improved were identified. These included addressing misunderstandings, tailoring the presentation of information to the patient's preferences, handling difficult questions, supporting emotional needs, and assessing the patient's understanding of their diagnosis and treatment.

7.
Eur Urol ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38688773

RESUMO

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (PCa) have been updated. Here we provide a summary of the 2024 guidelines. METHODS: The panel performed a literature review of new data, covering the time frame between 2020 and 2023. The guidelines were updated and a strength rating for each recommendation was added on the basis of a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. New treatment options, such as androgen receptor-targeted agents (ARTAs), ARTA + chemotherapy combinations, PARP inhibitors and their combinations, and prostate-specific membrane antigen-based therapy have become available for men with metastatic PCa. CONCLUSIONS AND CLINICAL IMPLICATIONS: Evidence for relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These guidelines reflect the multidisciplinary nature of PCa management. The full version is available online (http://uroweb.org/guideline/ prostate-cancer/). PATIENT SUMMARY: This article summarises the 2024 guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are based on evidence and guide doctors in discussing treatment decisions with their patients. The guidelines are updated every year.

8.
Addict Behav Rep ; 19: 100538, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38495390

RESUMO

Purpose: Individuals who do not complete substance use disorder treatment (SUDT) have similar outcomes to the untreated. Recovery capital (RC) is the collection of one's resources that contribute to the initiation and maintenance of sobriety. The aim of this paper was to identify individual measures of RC that are associated with SUDT completion. Methods: RC data for 69 residents from a men's recovery center was obtained from questionnaires administered to residents at intake and after SUDT graduation or dismissal. Participant data was divided into two groups, Graduates (n = 39, age 35.87±10.83) and Non-Graduates (n = 30, age 34.35±14.44), and retrospectively analyzed to compare RC between groups at various points during SUDT and which RC measures are associated with SUDT completion. Results: At baseline all participants reported limited RC and there was no significant difference in RC between groups. At graduation, Graduates reported significantly more RC in all measures when compared to baseline and Non-Graduates at dismissal. Non-Graduates reported a significant increase in Checking and Savings at dismissal but no other measure. Conclusion: Baseline levels of RC in both groups were limited and not significantly different which limited the capacity of the study to identify measures of RC associated with SUDT completion. A lack of RC at onset of SUDT did not preclude SUDT completion and obtaining RC during SUDT was associated with completion as only Graduates reported increases in RC. Future study designs should include participants with variable amounts of RC when entering SUDT.

9.
RSC Med Chem ; 15(3): 1015-1021, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516605

RESUMO

High throughput and rapid biological evaluation of small molecules is an essential factor in drug discovery and development. Direct-to-biology (D2B), whereby compound purification is foregone, has emerged as a viable technique in time efficient screening, specifically for PROTAC design and biological evaluation. However, one notable limitation is the prerequisite of high yielding reactions to ensure the desired compound is indeed the compound responsible for biological activity. Herein, we report a machine learning based yield-assay deconfounder capable of deconvoluting low yield from low potency to identify false negatives. We validated this approach by identifying promising SARS-CoV-2 main protease inhibitors with nanomolar activity that rivaled potency observed from the standard D2B workflow. Furthermore, we show how our framework can be utilized in a broad, in silico screen to produce compounds of similar potency as a D2B assay.

10.
JBMR Plus ; 8(4): ziae020, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38505820

RESUMO

Osteoporosis and associated fractures are an increasingly prevalent concern with an ageing population. This study reports testing of IBEX Bone Health (IBEX BH) software, applied following acquisition of forearm radiographs. IBEX Bone Health analyses the radiograph to measure areal bone mineral density (aBMD) at the examination site. A non-randomized cross-sectional study design was performed involving 261 (254 after exclusions) participants (112/142 m/f; mean age 70.8 years (SD+/-9.0); 53 with osteoporosis). They underwent posterior-anterior distal forearm radiographs; dual X-ray absorptiometry (DXA) of the wrists, hips, and lumbar spine; and questionnaires exploring clinical risk factors. IBEX Bone Health automatically identifies regions of interest (ROI) at the ultra-distal (UD) and distal third (TD) regions of the radius. Analysis investigated area under the receiver operating characteristics curve performance of IBEX BH for prediction of (i) osteoporosis (based on clinical reporting of the hip and spine DXA) and (ii) treatment recommendations by Fracture Risk Assessment Tool (FRAX) inclusive of neck of femur (NoF) areal bone mineral density (aBMD) results following National Osteoporosis Guideline Group (NOGG) guidelines. Area under the receiver operating characteristics curve for osteoporosis prediction at the UD and TD ROIs were 0.86 (99% confidence interval (CI) [0.80, 0.91]) and 0.81 (99% CI [0.75, 0.88]), respectively. Area under the receiver operating characteristics curve for treatment recommendation using FRAX inclusive of NoF aBMD at the UD and TD ROIs were 0.95 (99% CI [0.91, 1.00]) and 0.97 (99% CI [0.93,1.00]), respectively. With a matched sensitivity to FRAX (without NoF aBMD) 0.93 (99% CI [0.78, 0.99]), IBEX BH predicted at the UD and TD ROIs recommended treatment outcomes by NOGG guidelines using FRAX (with NoF aBMD) with specificity 0.89 (99% CI 0.83, 0.94]) and 0.93 (99% CI [0.87, 0.97]), respectively. This is compared with 0.60 (99% CI [0.51, 0.69]) for FRAX (without NoF aBMD). Results demonstrate the potential clinical utility of IBEX BH as an opportunistic screening tool.

11.
Eur Heart J Case Rep ; 8(3): ytae088, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38449779

RESUMO

Background: Congenital disorders of glycosylation (CDG) are rare genetically inherited defects leading to enzyme deficiency or malfunction in the glycosylation pathway. Normal glycosylation is essential to the development of normal cardiac anatomy and function. Congenital disorders of glycosylation-related cardiomyopathy are often the first manifestation detected in early life and may lead to sudden cardiac death. Approximately one-fifth of CDG types are related to cardiac diseases that include cardiomyopathy, rhythm disturbances, pericardial effusions, and structural heart disease. Case summary: We report a rare case of a 26-year-old lady with CDG-1 who presented with acute-onset dyspnoea. She had respiratory tract symptoms for the past 2 weeks. With the relevant clinical and biochemical findings, including supportive findings on echocardiogram and cardiac magnetic resonance imaging, we have managed to arrive at a diagnosis of severe pneumonia leading to acute decompensated heart failure, as well as the discovery of an underlying CDG-associated dilated cardiomyopathy (DCM) and acute myocarditis. Anti-failure medications and i.v. methylprednisolone were commenced, and she showed gradual clinical improvement with an increase of her left ventricular function. She was discharged home well with anti-failure therapy, prednisolone, and a follow-up echocardiogram with further review in the heart failure clinic. Discussion: In conclusion, this case report highlights the need for accurate diagnosis and prompt management of CDG-associated DCM, leading to a successful recovery and discharge from hospital care. With this, we hope to add to the increasing number of reported cases of CDG-related cardiac disease in the medical literature to emphasize the importance of screening and follow-up for any underlying cardiac diseases in patients with CDG.

12.
Soc Probl ; 71(1): 220-236, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38390287

RESUMO

Many LGBTQ adults have ongoing relationships with their parents that are ambivalent, typified by both solidarity (e.g., frequent contact, emotional or financial exchange) as well as conflict (e.g., parents' heterosexism and cissexism). Yet, why LGBTQ people remain in-rather than end-their ambivalent intergenerational ties is underexplored. We analyze qualitative in-depth interview data with 76 LGBTQ adults to answer this question. We find that LGBTQ adult children deploy narratives that privilege intergenerational solidarity over strain-what we call "solidarity rationales"- to explain why they remain in their ambivalent intergenerational ties. Four solidarity rationales were identified: 1) closeness and love, 2) parental growth, 3) the unique parent-child role, and 4) the importance of parental resources. Identifying LGBTQ adults' solidarity rationales pulls back the curtain on the compulsory social forces driving persistent intergenerational relationships. This study also advances our thinking about how socially marginalized people cope with complex social ties that include interpersonal discrimination and stigma.

13.
Am Heart J ; 271: 164-177, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38395294

RESUMO

BACKGROUND: Atrial fibrillation (AF) increases the risk of death, stroke, heart failure, cognitive decline, and healthcare costs but is often asymptomatic and undiagnosed. There is currently no national screening program for AF. The advent of validated hand-held devices allows AF to be detected in non-healthcare settings, enabling screening to be undertaken within the community. METHOD AND RESULTS: In this novel observational study, we embedded a MyDiagnostick single lead ECG sensor into the handles of shopping trolleys in four supermarkets in the Northwest of England: 2155 participants were recruited. Of these, 231 participants either activated the sensor or had an irregular pulse, suggesting AF. Some participants agreed to use the sensor but refused to provide their contact details, or consent to pulse assessment. In addition, some data were missing, resulting in 203 participants being included in the final analyses. Fifty-nine participants (mean age 73.6 years, 43% female) were confirmed or suspected of having AF; 20 were known to have AF and 39 were previously undiagnosed. There was no evidence of AF in 115 participants and the remaining 46 recordings were non-diagnostic, mainly due to artefact. Men and older participants were significantly more likely to have newly diagnosed AF. Due to the number of non-diagnostic ECGs (n = 46), we completed three levels of analyses, excluding all non-diagnostic ECGs, assuming all non-diagnostic ECGs were masking AF, and assuming all non-diagnostic ECGs were not AF. Based on the results of the three analyses, the sensor's sensitivity (95% CI) ranged from 0.70 to 0.93; specificity from 0.15 to 0.97; positive predictive values (PPV) and negative predictive values (NPV) ranged from 0.24 to 0.56 and 0.55 to 1.00, respectively. These values should be interpreted with caution, as the ideal reference standard on 1934 participants was imperfect. CONCLUSION: The study demonstrates that the public will engage with AF screening undertaken as part of their daily routines using hand-held devices. Sensors can play a key role in identifying asymptomatic patients in this way, but the technology must be further developed to reduce the quantity of non-diagnostic ECGs.


Assuntos
Fibrilação Atrial , Eletrocardiografia , Estudos de Viabilidade , Programas de Rastreamento , Humanos , Fibrilação Atrial/diagnóstico , Masculino , Feminino , Idoso , Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , Programas de Rastreamento/métodos , Programas de Rastreamento/instrumentação , Inglaterra , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
15.
Br J Clin Psychol ; 63(2): 227-243, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38288632

RESUMO

OBJECTIVES: Our aims were to examine whether an experiential course for care partners of people living with dementia, Empowered Conversations (EC), was acceptable to participants and to explore participants' perceptions of the impact of the course upon their communicative interactions. EC is based on an integrative model derived from psychological and linguistic theory and empirical evidence. EC is based on mentalisation theory, perceptual control theory and linguistic theory (The Communicative Impact Model). METHODS: Qualitative data were collected via 28 semistructured interviews. Framework analysis was used to analyse data. RESULTS: Three superordinate themes, 'improved communication', 'improved well-being' and 'support through others' were identified. Twenty-seven out of the 28 participants described feeling that they were able to better connect with the person living with dementia that they were supporting through attending EC. CONCLUSIONS: The findings indicated that EC was acceptable and beneficial to care partners. Care partners developed a range of strategies and understandings that enabled them to communicate better with the person they were supporting, enhanced well-being and relationships, as well as developing social networks. This is the first qualitative study to examine a psychosocial intervention for care partners of people living with dementia using a non-CBT framework and indicates that perceived control could influence how care partners respond to stress and difficulties.


Assuntos
Cuidadores , Comunicação , Demência , Pesquisa Qualitativa , Humanos , Demência/psicologia , Demência/terapia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Cuidadores/psicologia , Empoderamento , Idoso de 80 Anos ou mais , Adulto , Intervenção Psicossocial/métodos
16.
Nat Chem ; 16(4): 633-643, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38168924

RESUMO

High-throughput experimentation (HTE) has the potential to improve our understanding of organic chemistry by systematically interrogating reactivity across diverse chemical spaces. Notable bottlenecks include few publicly available large-scale datasets and the need for facile interpretation of these data's hidden chemical insights. Here we report the development of a high-throughput experimentation analyser, a robust and statistically rigorous framework, which is applicable to any HTE dataset regardless of size, scope or target reaction outcome, which yields interpretable correlations between starting material(s), reagents and outcomes. We improve the HTE data landscape with the disclosure of 39,000+ previously proprietary HTE reactions that cover a breadth of chemistry, including cross-coupling reactions and chiral salt resolutions. The high-throughput experimentation analyser was validated on cross-coupling and hydrogenation datasets, showcasing the elucidation of statistically significant hidden relationships between reaction components and outcomes, as well as highlighting areas of dataset bias and the specific reaction spaces that necessitate further investigation.

17.
BMJ Open ; 14(1): e076477, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38199617

RESUMO

INTRODUCTION: Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%-20%. Several iNTS vaccine candidates are in early-stage assessment which-if found effective-would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis. METHODS AND ANALYSIS: This double-blind, safety and dose-escalation study will randomise 40-80 healthy UK participants aged 18-50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%-75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host-pathogen interactions in response to infection. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Health Research Authority (London-Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants. TRIAL REGISTRATION NUMBER: NCT05870150.


Assuntos
Canto , Febre Tifoide , Vacinas , Humanos , Salmonella , Londres , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Qual Health Res ; : 10497323231217601, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38205737

RESUMO

Photovoice is a type of visual research method which supports participants to reflect upon their experiences by capturing digital images. It is a methodology that is routinely used with groups that could be considered vulnerable, as a way of allowing participants to tell their stories for themselves. This article details the process of conducting a Photovoice study with individuals in recovery from problem substance use and reflects on the methodological benefits and challenges of utilising a visual research methodology with this population. Researchers wishing to conduct a Photovoice study with individuals in recovery should be mindful of striking a delicate balance between respecting an individual's autonomy and ensuring their wellbeing. Although ethically complex, Photovoice is an ideal method for research with this population as it allows participants to convey meaning and introduce narratives for themselves in an engaging way.

19.
Glob Health Action ; 17(1): 2302208, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38224051

RESUMO

BACKGROUND: Assistive technology is central to the realization of the rights of persons with disabilities. However, there remains limited access to assistive technology throughout much of the world, with particularly poor access in lower- and middle-income countries. Evaluating stakeholder engagement in assistive technology networks has been used as a successful strategy to understand and address gaps in the assistive technology ecosystem. OBJECTIVE: The objective of this research was to provide an overview of the Kenyan Assistive Technology Ecosystem, including available assistive products and related services, and an understanding of the nature and strength of relationships between stakeholders. METHODS: In this study, we employed an online qualitative stakeholder survey (2021) with representatives of organizations involved in assistive technology in Kenya. RESULTS: The assistive technology network in Kenya is distributed, with Government Ministries and Agencies and Organizations of persons with disabilities central to the network. The strength of relationships is concentrated on awareness and communication, with fewer organizations actively collaborating. Innovation training organizations are not yet well integrated into the network. CONCLUSIONS: Improving access to assistive technology in Kenya will benefit from greater collaboration amongst all assistive technology stakeholders.


Assuntos
Pessoas com Deficiência , Tecnologia Assistiva , Humanos , Quênia , Ecossistema , Comunicação
20.
Nat Commun ; 15(1): 426, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225239

RESUMO

Structural diversification of lead molecules is a key component of drug discovery to explore chemical space. Late-stage functionalizations (LSFs) are versatile methodologies capable of installing functional handles on richly decorated intermediates to deliver numerous diverse products in a single reaction. Predicting the regioselectivity of LSF is still an open challenge in the field. Numerous efforts from chemoinformatics and machine learning (ML) groups have made strides in this area. However, it is arduous to isolate and characterize the multitude of LSF products generated, limiting available data and hindering pure ML approaches. We report the development of an approach that combines a message passing neural network and 13C NMR-based transfer learning to predict the atom-wise probabilities of functionalization for Minisci and P450-based functionalizations. We validated our model both retrospectively and with a series of prospective experiments, showing that it accurately predicts the outcomes of Minisci-type and P450 transformations and outperforms the well-established Fukui-based reactivity indices and other machine learning reactivity-based algorithms.


Assuntos
Descoberta de Drogas , Redes Neurais de Computação , Estudos Prospectivos , Estudos Retrospectivos , Descoberta de Drogas/métodos , Aprendizado de Máquina
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