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1.
Victoria L. Parker Matthew C. Winter John A. Tidy Barry W. Hancock Julia E. Palmer Naveed Sarwar Baljeet Kaur Katie McDonald Xianne Aguiar Kamaljit Singh Nick Unsworth Imran Jabbar Allan A. Pacey Robert F. Harrison Michael J. Seckl 《International journal of cancer. Journal international du cancer》2023,152(5):986-997
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus. 相似文献
2.
Lauren Tingey Britta Mullany Rachel Chambers Ranelda Hastings Angelita Lee Anthony Parker 《AIDS care》2015,27(9):1087-1097
Potential for widespread transmission of HIV/AIDS among American Indian (AI) adolescents exists, yet no evidence-based interventions (EBIs) have been adapted and evaluated with this population. Intensive psychoeducation may improve knowledge and decision-making which could potentially translate to reductions in HIV risk behaviors. A peer group randomized controlled comparison of an adapted EBI vs. control was delivered over an eight-day summer basketball camp in one reservation-based tribal community to adolescents ages 13–19. Outcome data were gathered immediately post-camp and at 6 and 12 months follow-up. Self-selected peer groups were randomized to intervention (n = 138) or control (n = 129) conditions for a total sample of 267 participants (56.2% female), mean age 15.1 years (SD = 1.7). Intervention participants had better condom use self-efficacy post-camp (Adjusted Mean Difference [AMD] = ?0.75, p < 0.005) and at 6 (AMD = ?0.44, p < 0.005) and 12 months (AMD = ?0.23, p < 0.05) follow-up. Intervention participants also had higher HIV prevention and transmission knowledge (post-camp: AMD = 0.07, p < 0.01; 6 months: AMD = 0.06, p < 0.01) were more likely to believe condoms prevent sexually transmitted infections (post-camp: RR = 1.41, p < 0.005; 6 months: RR = 1.34, p < 0.05), to talk with an adult about HIV/AIDS (post-camp: RR=1.78, p < 0.005; 6 months: RR = 1.14, p < 0.005), had higher partner negotiation efficacy related to substance use during sex (post-camp: AMD = 0.37, p < 0.01), and were more likely to intend to use a condom (post-camp: RR = 1.39, p < 0.01). The adapted intervention had short- and medium-term impacts on AI adolescent risk for HIV/AIDS, but attenuated at 12 months. Intervention delivery through a community-based camp is feasible and acceptable with strong retention. Additional study is needed to evaluate the adapted intervention's impact on sexual risk behaviors and if booster sessions and parent involvement translate to long-term impacts. 相似文献
3.
Jeffrey Buenaflor Parker Sommerville Hang Qian Christine Luscombe 《Macromolecular chemistry and physics.》2020,221(2)
A comparative study involving bimetallic nickel catalysts designed from disubstituted N,N,N′,N′‐tetra(diphenylphosphanylmethyl)benzene diamine bridging ligands is reported. Catalyst behavior is explored in the Kumada catalyst‐transfer polymerization (KCTP) using poly(3‐hexylthiophene) (P3HT) as the model system. The success of a controlled polymerization is monitored by analyzing monomer conversion, degree of polymerization, end‐group identity, and molecular weight distribution. The characterization of P3HT obtained from KCTP initiated with the bimetallic catalysts shows chain‐growth behavior; however, the presence of Br/Br end‐groups and broader molecular weight distribution reveals a reduced controlled polymerization compared to the commonly employed Ni(dppp)Cl2. The observed increase in intermolecular chain transfer and termination processes in KCTP initiation with the bimetallic catalysts can be attributed to a weaker Ni(0)‐π‐aryl complex interaction, which is caused by increased steric crowding of the coordination sphere. 相似文献
4.
Purpose
Chest wall pain is an uncommon but bothersome late complication following lung stereotactic body radiation therapy. Despite numerous studies investigating predictors of chest wall pain, no clear consensus has been established for a chest wall constraint. The aim of our study was to investigate factors related to chest wall pain in a homogeneous group of patients treated at our institution.Patients and methods
All 122 patients were treated with the same stereotactic body radiation therapy regimen of 48 Gy in three fractions, seen for at least 6 months of follow-up, and planned with heterogeneity correction. Chest wall pain was scored according to the Common Terminology Criteria for Adverse Events classification v3.0. Patient (age, sex, diabetes, osteoporosis), tumour (planning target volume, volume of the overlapping region between planning target volume and chest wall) and chest wall dosimetric parameters (volumes receiving at least 30, 40, and 50 Gy, the minimal doses received by the highest irradiated 1, 2, and 5 cm3, and maximum dose) were collected. The correlation between chest wall pain (grade 2 or higher) and the different parameters was evaluated using univariate and multivariate logistic regression.Results
Median follow-up was 18 months (range: 6–56 months). Twelve patients out of 122 developed chest wall pain of any grade (seven with grade 1, three with grade 2 and two with grade 3 pain). In univariate analysis, only the volume receiving 30 Gy or more (P = 0.034) and the volume of the overlapping region between the planning target volume and chest wall (P = 0.038) significantly predicted chest wall pain, but these variables were later proved non-significant in multivariate regression.Conclusion
Our analysis could not find any correlation between the studied parameters and chest wall pain. Considering our present study and the wide range of differing results from the literature, a reasonable conclusion is that a constraint for chest wall pain is yet to be defined. 相似文献5.
Dynamic LVOT Obstruction and Aortic Stenosis in the Same Patient: A Case of Challenging Doppler Hemodynamics 下载免费PDF全文
Matthew W. Parker M.D. Francis J. Kiernan M.D. 《Echocardiography (Mount Kisco, N.Y.)》2015,32(6):1030-1032
We present a patient with both dynamic left ventricular outflow tract obstruction and valvular aortic stenosis. The aortic valve was calcified, and velocities and gradients measured by continuous‐wave Doppler met standard criteria for severe aortic stenosis. The increased subvalvular velocities invalidated assumptions of the simplified Bernoulli equation; correction using the longer form of the Bernoulli equation suggested a lower but still significant gradient. The complex shape of the subvalvular spectral Doppler envelope indicated supranormal systolic function and dynamic left ventricular outflow obstruction. Left heart catheterization with an end‐hole catheter was required to determine the subvalvular and valvular components of the obstruction. 相似文献
6.
Henry Havel Gregory Finch Pamela Strode Marc Wolfgang Stephen Zale Iulian Bobe Hagop Youssoufian Matthew Peterson Maggie Liu 《The AAPS journal》2016,18(6):1373-1378
Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements—only together can they realize the full potential of nanomedicines for patients. 相似文献
7.
8.
Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease
Abhinav Sharma Adrian Coles Nishant K. Sekaran Neha J. Pagidipati Michael T. Lu Daniel B. Mark Kerry L. Lee Hussein R. Al-Khalidi Udo Hoffmann Pamela S. Douglas 《Journal of the American College of Cardiology》2019,73(8):893-902
Background
The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.Objectives
The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.Methods
PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.Results
Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).Conclusions
In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550) 相似文献9.
Catherine L. Omosule Dominique Joseph Brooke Weiler Victoria L. Gremminger Spencer Silvey Youngjae Jeong Ashique Rafique Pamela Krueger Sandra Kleiner Charlotte L. Phillips 《Journal of bone and mineral research》2022,37(5):938-953
Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-β (TGF-β) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro–computed tomography (μCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR). 相似文献
10.