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1.
Phys Rev Lett ; 132(9): 095101, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489653

RESUMO

Electrostatic waves play a critical role in nearly every branch of plasma physics from fusion to advanced accelerators, to astro, solar, and ionospheric physics. The properties of planar electrostatic waves are fully determined by the plasma conditions, such as density, temperature, ionization state, or details of the distribution functions. Here we demonstrate that electrostatic wave packets structured with space-time correlations can have properties that are independent of the plasma conditions. For instance, an appropriately structured electrostatic wave packet can travel at any group velocity, even backward with respect to its phase fronts, while maintaining a localized energy density. These linear, propagation-invariant wave packets can be constructed with or without orbital angular momentum by superposing natural modes of the plasma and can be ponderomotively excited by space-time structured laser pulses like the flying focus.

2.
Opt Express ; 31(19): 31354-31368, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710657

RESUMO

"Flying focus" techniques produce laser pulses with dynamic focal points that travel distances much greater than a Rayleigh length. The implementation of these techniques in laser-based applications requires the design of optical configurations that can both extend the focal range and structure the radial group delay. This article describes a method for designing optical configurations that produce ultrashort flying focus pulses with programmable-trajectory focal points. The method is illustrated by several examples that employ an axiparabola for extending the focal range and either a reflective echelon or a deformable mirror-spatial light modulator pair for structuring the radial group delay. The latter configuration enables rapid exploration and optimization of flying foci, which could be ideal for experiments.

3.
Ann Oncol ; 34(10): 899-906, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37597579

RESUMO

BACKGROUND: We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy. PATIENTS AND METHODS: We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence. RESULTS: Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10-4 (range 7.9 × 10-7-4.9 × 10-1). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12. CONCLUSIONS: Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , DNA Tumoral Circulante/genética , Terapia Neoadjuvante/efeitos adversos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasia Residual/genética , Neoplasia Residual/patologia , Estudos Prospectivos , Neoplasias da Mama/etiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética
4.
Child Abuse Negl ; : 106335, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37400323

RESUMO

BACKGROUND: War and violence have a serious negative impact on the wellbeing and mental health of many children. Caregivers play an important role in mitigating or exacerbating this impact. OBJECTIVE: This study evaluates the impact of the nine session Caregiver Support Intervention on improving children's wellbeing and examines putative mediators of changes in children's psychosocial wellbeing. PARTICIPANTS AND SETTING: 240 female caregivers were randomly allocated (1:1) to the CSI or a waitlist control comparison condition. The study was implemented in Lebanon, in an area characterized by high levels of poverty and a high number of the Syrian refugees. METHODS: A parallel group Randomized Controlled Trial reporting on caregiver-reported child-level wellbeing. We used a combination of the Kid- and Kiddy-KINDL (parent version) for index children ages three to 12. Putative mediators of the CSI on children's psychosocial wellbeing included harsh parenting, caregiver psychological distress, caregiver wellbeing. Measurements were conducted at baseline, post-intervention and 3-months follow-up. RESULTS: We demonstrated a statistically significant change in caregiver reported children's psychosocial wellbeing at post-intervention (Mdiff =4.39, 95 % CI = 1.12, 7.65, p < 0.01, d = 0.28) but not at follow-up (Mdiff = -0.97, 95 % CI = -4.27, 2.32, p > 0.05). The proportion of the total effect of the CSI intervention on child psychosocial wellbeing mediated by caregiver distress, caregiver wellbeing and harsh parenting was 77 %. CONCLUSION: The CSI holds potential for down-stream short-term effect on improving children's psychosocial wellbeing, beyond the previously reported positive caregiver outcomes. This effect was not sustained three months post intervention. The study confirms caregiver wellbeing and parenting support as dual pathways mediating child psychosocial wellbeing. Prospective trial registration: ISRCTN22321773.

5.
J Anim Ecol ; 92(9): 1840-1855, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37415521

RESUMO

Predation risk and prey responses exhibit fluctuations in space and time. Seasonal ecological disturbances can alter landscape structure and permeability to influence predator activity and efficacy, creating predictable patterns of risk for prey (seasonal risk landscapes). This may create corresponding seasonal shifts in antipredator behaviour, mediated by species ecology and trade-offs between risk and resources. Yet, how human recreation interacts with seasonal risk landscapes and antipredator behaviour remains understudied. In South Florida, we investigated the impact of a seasonal ecological disturbance, specifically flooding, which is inversely related to human activity, on interactions between Florida panthers (Puma concolor coryi) and white-tailed deer (Odocoileus virginianus). We hypothesized that human activity and ecological disturbances would interact with panther-deer ecology, resulting in the emergence of two distinct seasonal landscapes of predation risk and the corresponding antipredator responses. We conducted camera trap surveys across southwestern Florida to collect detection data on humans, panthers and deer. We analysed the influence of human site use and flooding on deer and panther detection probability, co-occurrence and diel activity during the flooded and dry seasons. Flooding led to decreased panther detections and increased deer detections, resulting in reduced deer-panther co-occurrence during the flooded season. Panthers exhibited increased nocturnality and reduced diel activity overlap with deer in areas with higher human activity. Supporting our hypothesis, panthers' avoidance of human recreation and flooding created distinct risk schedules for deer, driving their antipredator behaviour. Deer utilized flooded areas to spatially offset predation risk during the flooded season while increasing diurnal activity in response to human recreation during the dry season. We highlight the importance of understanding how competing risks and ecological disturbances influence predator and prey behaviour, leading to the generation of seasonal risk landscapes and antipredator responses. We emphasize the role of cyclical ecological disturbances in shaping dynamic predator-prey interactions. Furthermore, we highlight how human recreation may function as a 'temporal human shield,' altering seasonal risk landscapes and antipredator responses to reduce encounter rates between predators and prey.


Assuntos
Cervos , Puma , Humanos , Animais , Cervos/fisiologia , Estações do Ano , Comportamento Predatório/fisiologia , Puma/fisiologia , Chuva , Recreação , Ecossistema
6.
Clin Oncol (R Coll Radiol) ; 35(9): e549-e560, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321887

RESUMO

AIMS: This study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. MATERIALS AND METHODS: The study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I-IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. RESULTS: Among 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3-77.3%), but varied less for the high-risk (range 77.1-91.6%) and low-risk groups (range 4.1-32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. CONCLUSIONS: Rates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.


Assuntos
Neoplasias da Mama , Fragilidade , Feminino , Humanos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Inglaterra/epidemiologia , Mastectomia , Medicina Estatal , País de Gales/epidemiologia , Pessoa de Meia-Idade
7.
Sci Total Environ ; 891: 164060, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37230344

RESUMO

The feeding of wild birds is a popular but often controversial activity. This study explored differences in demographics, attitudes, and normative beliefs between waterbird feeders and non-feeders at an urban wetland residential estate in Melbourne, Australia. An online survey of nearby residents and visitors (n = 206) identified those who have fed waterbirds at least once in the past two years (feeders; 32.4 %) and those who have not (non-feeders). No differences were observed in demographic profile or connection to nature between feeders and non-feeders, but feeders were significantly more likely to believe that waterbird feeding is an acceptable activity. When compared with non-feeders, feeders exhibited different injunctive and descriptive norms relating to waterbird feeding; feeders believed that most people would be relatively happy with them feeding waterbirds in their community, while non-feeders thought that most people would be moderately unhappy. Feeders believed that more than half of the people in their community fed waterbirds (55.5 %), while non-feeders believed that less than half fed birds (36.7 %). These findings suggest that education or behaviour change programs with bird feeding objectives could be enhanced with information about the actual and perceived social norms for this common activity.


Assuntos
Aves , Áreas Alagadas , Animais , Austrália , Demografia , Inquéritos e Questionários
8.
Osteoarthritis Cartilage ; 31(7): 954-965, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36893979

RESUMO

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.


Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Quadril/terapia , Consenso , Pessoal de Saúde , Inquéritos e Questionários , Técnica Delphi
9.
Clin Oncol (R Coll Radiol) ; 35(4): e265-e277, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36764877

RESUMO

AIMS: Clinical trials of post-mastectomy radiotherapy (PMRT) for early invasive breast cancer (EIBC) have included few older women. This study examined whether the association between overall survival or breast cancer-specific survival (BCSS) and receipt of PMRT for EIBC altered with age. MATERIALS AND METHODS: The study used patient-level linked cancer registration, routine hospital and radiotherapy data for England and Wales. It included 31 243 women aged ≥50 years diagnosed between 2014 and 2018 with low- (T1-2N0), intermediate- (T3N0/T1-2N1) or high-risk (T1-2N2/T3N1-2) EIBC who received a mastectomy within 12 months from diagnosis. Patterns of survival were analysed using a landmark approach. Associations between overall survival/BCSS and PMRT in each risk group were analysed with flexible parametric survival models, which included patient and tumour factors; whether the association between PMRT and overall survival/BCSS varied by age was assessed using interaction terms. RESULTS: Among 4711 women with high-risk EIBC, 86% had PMRT. Five-year overall survival was 70.5% and BCSS was 79.3%. Receipt of PMRT was associated with improved overall survival [adjusted hazard ratio (aHR) 0.75, 95% confidence interval 0.64-0.87] and BCSS (aHR 0.78, 95% confidence interval 0.65-0.95) compared with women who did not have PMRT; associations did not vary by age (overall survival, P-value for interaction term = 0.141; BCSS, P = 0.077). Among 10 814 women with intermediate-risk EIBC, 59% had PMRT; 5-year overall survival was 78.4% and BCSS was 88.0%. No association was found between overall survival (aHR 1.01, 95% confidence interval 0.92-1.11) or BCSS (aHR 1.16, 95% confidence interval 1.01-1.32) and PMRT. There was statistical evidence of a small change in the association with age for overall survival (P = 0.007), although differences in relative survival were minimal, but not for BCSS (P = 0.362). CONCLUSIONS: The association between PMRT and overall survival/BCSS does not appear to be modified by age among women with high- or intermediate-risk EIBC and, thus, treatment recommendations should not be modified on the basis of age alone.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Estudos de Coortes , Radioterapia Adjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos
10.
Anaesthesia ; 78(4): 458-478, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36630725

RESUMO

Human factors is an evidence-based scientific discipline used in safety critical industries to improve safety and worker well-being. The implementation of human factors strategies in anaesthesia has the potential to reduce the reliance on exceptional personal and team performance to provide safe and high-quality patient care. To encourage the adoption of human factors science in anaesthesia, the Difficult Airway Society and the Association of Anaesthetists established a Working Party, including anaesthetists and operating theatre team members with human factors expertise and/or interest, plus a human factors scientist, an industrial psychologist and an experimental psychologist/implementation scientist. A three-stage Delphi process was used to formulate a set of 12 recommendations: these are described using a 'hierarchy of controls' model and classified into design, barriers, mitigations and education and training strategies. Although most anaesthetic knowledge of human factors concerns non-technical skills, such as teamwork and communication, human factors is a broad-based scientific discipline with many other additional aspects that are just as important. Indeed, the human factors strategies most likely to have the greatest impact are those related to the design of safe working environments, equipment and systems. While our recommendations are primarily provided for anaesthetists and the teams they work with, there are likely to be lessons for others working in healthcare beyond the speciality of anaesthesia.


Assuntos
Anestesia , Anestesiologia , Médicos , Humanos , Anestesiologia/educação , Anestesistas , Hospitais
11.
Anaesthesia ; 78(4): 479-490, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36630729

RESUMO

Healthcare relies on high levels of human performance, as described by the 'human as the hero' concept. However, human performance varies and is recognised to fall in high-pressure situations, meaning that it is not a reliable method of ensuring safety. Other safety-critical industries embed human factors principles into all aspects of their organisations to improve safety and reduce reliance on exceptional human performance; there is potential to do the same in anaesthesia. Human factors is a broad-based scientific discipline which aims to make it as easy as possible for workers to do things correctly. The human factors strategies most likely to be effective are those which 'design out' the chance of an error or adverse event occurring. When errors or adverse events do happen, barriers are in place to trap them and reduce the risk of progression to patient and/or worker harm. If errors or adverse events are not trapped by these barriers, mitigations are in place to minimise the consequences. Non-technical skills form an important part of human factors barriers and mitigation strategies and include: situation awareness; decision-making; task management; and team working. Human factors principles are not a substitute for proper investment and appropriate staffing levels. Although applying human factors science has the potential to save money in the long term, its proper implementation may require investment before reward can be reaped. This narrative review describes what is known about human factors in anaesthesia to date.


Assuntos
Anestesia , Anestesiologia , Humanos , Anestesia/efeitos adversos
13.
Epidemiol Psychiatr Sci ; 31: e75, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36245402

RESUMO

Mental disorders are one of the largest contributors to the burden of disease globally, this holds also for children and adolescents, especially in low- and middle-income countries. The prevalence and severity of these disorders are influenced by social determinants, including exposure to adversity. When occurring early in life, these latter events are referred to as adverse childhood experiences (ACEs).In this editorial, we provide an overview of the literature on the role of ACEs as social determinants of mental health through the lenses of global mental health. While the relation between ACEs and mental health has been extensively explored, most research was centred in higher income contexts. We argue that findings from the realm of global mental health should be integrated into that of ACEs, e.g. through preventative and responsive psychosocial interventions for children, adolescents and their caregivers. The field of global mental health should also undertake active efforts to better address ACEs in its initiatives, all with the goal of reducing the burden of mental disorders among children and adolescents globally.


Assuntos
Experiências Adversas da Infância , Transtornos Mentais , Adolescente , Criança , Humanos , Renda , Transtornos Mentais/epidemiologia , Saúde Mental , Taurina/análogos & derivados
14.
Urologie ; 61(9): 971-981, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-35925101

RESUMO

PURPOSE: In a systematic data analysis, we evaluated the influence of a digital health app on erection scores as well as life quality and patient activation in a group of patients with erectile dysfunction. METHODS: In all, 44 participants took part in an evidence-based program for patients with erectile dysfunction. The in app 12-week program included pelvic floor exercises and physiotherapeutic and cardiovascular training. In addition, there where sessions on mindfulness and sexual therapy as well as useful information about erectile dysfunction and its causes, nutrition, and risk factors. The median age was 46 years (19-75 years). All patients answered IIEF­5, PAM-13 and QoL-Med questionnaires at the beginning and the end of the program. A total of 27 questionnaires could be evaluated at both times. RESULTS: The average improvement in IIEF­5 score was 4.5 points (p < 0.0001). 96% of patients showed overall improvement of erection scores. Improvement in life quality was shown in 93% of participants. Moreover, there was a significant increase in patient activation scores. CONCLUSION: We were able to show that a multimodal digital app for self-management of erectile dysfunction improved not only erection scores but also life quality and patient activation. We concluded that it is possible to reproduce results of analog studies in a digital setting. Digital solutions can help to include patients in their treatment and to put guideline suggestions into practice.


Assuntos
Disfunção Erétil , Aplicativos Móveis , Disfunção Erétil/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/fisiologia , Qualidade de Vida , Resultado do Tratamento
15.
Clin Oncol (R Coll Radiol) ; 34(9): e400-e409, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35691761

RESUMO

AIMS: Adjuvant radiotherapy is recommended for most patients with early breast cancer (EBC) receiving breast-conserving surgery and those at moderate/high risk of recurrence treated by mastectomy. During the first wave of COVID-19 in England and Wales, there was rapid dissemination of randomised controlled trial-based evidence showing non-inferiority for five-fraction ultra-hypofractionated radiotherapy (HFRT) regimens compared with standard moderate-HFRT, with guidance recommending the use of five-fraction HFRT for eligible patients. We evaluated the uptake of this recommendation in clinical practice as part of the National Audit of Breast Cancer in Older Patients (NABCOP). MATERIALS AND METHODS: Women aged ≥50 years who underwent surgery for EBC from January 2019 to July 2020 were identified from the Rapid Cancer Registration Dataset for England and from Wales Cancer Network data. Radiotherapy details were from linked national Radiotherapy Datasets. Multivariate mixed-effects logistic regression models were used to assess characteristics influential in the use of ultra-HFRT. RESULTS: Among 35 561 women having surgery for EBC, 71% received postoperative radiotherapy. Receipt of 26 Gy in five fractions (26Gy5F) increased from <1% in February 2020 to 70% in April 2020. Regional variation in the use of 26Gy5F during April to July 2020 was similar by age, ranging from 49 to 87% among women aged ≥70 years. Use of 26Gy5F was characterised by no known nodal involvement, no comorbidities and initial breast-conserving surgery. Of those patients receiving radiotherapy to the breast/chest wall, 85% had 26Gy5F; 23% had 26Gy5F if radiotherapy included regional nodes. Among 5139 women receiving postoperative radiotherapy from April to July 2020, nodal involvement, overall stage, type of surgery, time from diagnosis to start of radiotherapy were independently associated with fractionation choice. CONCLUSIONS: There was a striking increase in the use of 26Gy5F dose fractionation regimens for EBC, among women aged ≥50 years, within a month of guidance published at the start of the COVID-19 pandemic in England and Wales.


Assuntos
Neoplasias da Mama , COVID-19 , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Pandemias , Radioterapia Adjuvante/efeitos adversos , País de Gales/epidemiologia
16.
Chem Commun (Camb) ; 58(37): 5590-5593, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35441618

RESUMO

Polymer networks crosslinked with spring-like ortho-phenylene (oP) foldamers were developed. NMR analysis indicated the oP crosslinkers were well-folded. Polymer networks with oP-based crosslinkers showed enhanced energy dissipation and elasticity compared to divinylbenzene crosslinked networks. The energy dissipation was attributed to the strain-induced reversible unfolding of the oP units. Energy dissipation increased with the number of helical turns in the foldamer.


Assuntos
Polímeros , Espectroscopia de Ressonância Magnética , Polímeros/química
18.
Breast Cancer Res Treat ; 192(2): 235-243, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34973083

RESUMO

PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.


Assuntos
Neoplasias da Mama , Neoplasias Inflamatórias Mamárias , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/diagnóstico , Neoplasias Inflamatórias Mamárias/epidemiologia , Neoplasias Inflamatórias Mamárias/terapia
19.
Cereb Cortex ; 32(12): 2555-2574, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34730185

RESUMO

Noninvasive diffusion-weighted magnetic resonance imaging (dMRI) can be used to map the neural connectivity between distinct areas in the intact brain, but the standard resolution achieved fundamentally limits the sensitivity of such maps. We investigated the sensitivity and specificity of high-resolution postmortem dMRI and probabilistic tractography in rhesus macaque brains to produce retinotopic maps of the lateral geniculate nucleus (LGN) and extrastriate cortical visual area V5/MT based on their topographic connections with the previously established functional retinotopic map of primary visual cortex (V1). We also replicated the differential connectivity of magnocellular and parvocellular LGN compartments with V1 across visual field positions. Predicted topographic maps based on dMRI data largely matched the established retinotopy of both LGN and V5/MT. Furthermore, tractography based on in vivo dMRI data from the same macaque brains acquired at standard field strength (3T) yielded comparable topographic maps in many cases. We conclude that tractography based on dMRI is sensitive enough to reveal the intrinsic organization of ordered connections between topographically organized neural structures and their resultant functional organization.


Assuntos
Córtex Visual , Vias Visuais , Animais , Imagem de Difusão por Ressonância Magnética , Corpos Geniculados/diagnóstico por imagem , Macaca mulatta , Córtex Visual/diagnóstico por imagem , Vias Visuais/diagnóstico por imagem
20.
Anal Bioanal Chem ; 414(1): 675-689, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34651209

RESUMO

The application of Ca isotopic analysis in biomedical studies has great potential to identify changes in Ca metabolism and bone metabolism. Reliable measurement of Ca isotope-amount ratios is challenging considering limited Ca amounts and significant procedural blank levels. In this study, Ca purification was performed using the DGA Resin, optimized for low procedural blanks and separation of Ca from matrix elements and isobaric interferences (Na, Mg, K, Ti, Fe, Ba), while maintaining quasi-quantitative recoveries which are sufficient since a 42Ca-48Ca double-spike (DS) was applied. Ca isotopic analysis was performed using multicollector thermal ionization mass spectrometry (MC TIMS). The obtained procedural Ca blank of ≤10 ng enables processing of limited Ca amounts down to 670 ng. Data reduction of the measured Ca isotope-amount ratios was performed using an in-house developed software solving the DS algorithm. Data quality was improved by extension of equilibration time of the sample-DS mixture and implementation of a normalization strategy for raw isotopic data. The reported δ(44Ca/40Ca)NIST SRM 915a of NIST SRM 915a processed as a sample was found to be 0.01 ‰ ± 0.08 ‰ (2 SD, n = 15). Ca isotope-amount ratios of the reference material NIST SRM 1400 (bone ash), NIST SRM 1486 (bone meal), GBW07601 (human hair), and IAPSO (seawater) were in good agreement within uncertainty with literature data. Novel data on additional reference materials for biological tissues (hair) is presented, which might indicate a potential fractionation of Ca incorporated into hair tissue when compared to the blood pool.


Assuntos
Fracionamento Químico , Isótopos , Cabelo/química , Humanos , Isótopos/análise , Espectrometria de Massas/métodos
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