Generalised estimating equations with the sandwich standard-error estimator provide a promising method of analysis for stepped wedge cluster randomised trials. However, they have inflated type-one error when used with a small number of clusters, which is common for stepped wedge cluster randomised trials. We present a large simulation study of binary outcomes comparing bias-corrected standard errors from Fay and Graubard; Mancl and DeRouen; Kauermann and Carroll; Morel, Bokossa, and Neerchal; and Mackinnon and White with an independent and exchangeable working correlation matrix. We constructed 95% confidence intervals using a t-distribution with degrees of freedom including clusters minus parameters (DFC-P), cluster periods minus parameters, and estimators from Fay and Graubard (DFFG), and Pan and Wall. Fay and Graubard and an approximation to Kauermann and Carroll (with simpler matrix inversion) were unbiased in a wide range of scenarios with an independent working correlation matrix and more than 12 clusters. They gave confidence intervals with close to 95% coverage with DFFG with 12 or more clusters, and DFC-P with 18 or more clusters. Both standard errors were conservative with fewer clusters. With an exchangeable working correlation matrix, approximated Kauermann and Carroll and Fay and Graubard had a small degree of under-coverage.Peste des petits ruminants (PPR) in Africa continues to defy conventional vaccinational approaches aimed at its control. https://www.selleckchem.com/products/4-hydroxytamoxifen-4-ht-afimoxifene.html There is need for route modification and immunopotentiation of the current vaccination methods, using easily affordable materials. This study evaluates the immunomodulatory potential of Irvingia gabonensis (IG) seed gum extract for intranasal PPR vaccination in goats using attenuated Nigeria 75/1 PPR vaccine. Twenty West African dwarf goats were divided into four groups (n=5). Group 1 was vaccinated intranasally using IG gum as vehicle; Group 2 was vaccinated intranasally without the gum; Group 3 via subcutaneous injection while Group 4 was not vaccinated. Hematology and Serum IgG levels were assessed weekly for 28 days post vaccination (dpv). H-PPR bELISA detected antibodies against PPR by 7th dpv, peaking by 21st dpv with mean percentage inhibitions of 78.2%; 69.6%; 87.0% and 0% in Groups 1, 2, 3 and 4, respectively. Also, significantly lower neutrophil to lymphocyte ratio (P less then 0.05) were observed by 14th dpv to 28th dpv in the vaccinated groups. The findings of this study show that the use of I. gabonensis seed gum extract for mucoadhesive intranasal PPR vaccine delivery has an immunomodulatory effect on the systemic immune response following PPR intranasal vaccine administration. To identify the approximately 12% with inherited cancer predisposition, all men with metastatic prostate cancer (mPC) should be offered germline genetic testing. This guides treatment choices and impacts cancer prevention in the family. Limited genetic services globally present a barrier to testing. This study tested a potential solution, "mainstreaming," where counseling and testing are performed by the patient's oncologist. Men with mPC at three Australian sites were offered germline genetic testing at their medical oncology appointment. Panel testing ( , , , , , , , , , , , , , , , and ) was performed on saliva/blood (Invitae, San Francisco, CA). Primary outcomes were clinician and patient satisfaction. Secondary outcomes included mutation rates and resource allocation. Of 66 men offered testing, 63 (95%) accepted. Four pathogenic variants were identified (two , one , and one ). Fifty patients and nine clinicians completed questionnaires. Satisfaction was high. All patients were pleased to have had testing overall, 98% (46 of 47) to have had testing at their usual oncology appointment, and all to receive results from their usual specialist, rather than a separate genetics appointment. A total of 88% (7 of 8) of clinicians felt confident, and all were satisfied with mainstreaming. Mainstreaming was resource efficient, requiring 87% fewer genetic consultations than traditional genetic counseling. This study demonstrates that mainstreaming of men with mPC is feasible, resource efficient, and satisfactory for clinicians and patients. Widespread implementation as standard of care would facilitate timely access to genetic testing for men with mPC. This study demonstrates that mainstreaming of men with mPC is feasible, resource efficient, and satisfactory for clinicians and patients. Widespread implementation as standard of care would facilitate timely access to genetic testing for men with mPC.The mixture cure model has been widely applied to survival data in which a fraction of the observations never experience the event of interest, despite long-term follow-up. In this paper, we study the Cox proportional hazards mixture cure model where the covariate effects on the distribution of uncured subjects' failure time may jump when a covariate exceeds a change point. The nonparametric maximum likelihood estimation is used to obtain the semiparametric estimates. We employ a two-step computational procedure involving the Expectation-Maximization algorithm to implement the estimation. The consistency, convergence rate and asymptotic distributions of the estimators are carefully established under technical conditions and we show that the change point estimator is n consistency. The m out of n bootstrap and the Louis algorithm are used to obtain the standard errors of the estimated change point and other regression parameter estimates, respectively. We also contribute a test procedure to check the existence of the change point. The finite sample performance of the proposed method is demonstrated via simulation studies and real data examples.To calculate sample sizes in cluster randomized trials (CRTs), the cluster sizes are usually assumed to be identical across all clusters for simplicity. However, equal cluster sizes are not guaranteed in practice, especially when the number of clusters is limited. Therefore, it is important to understand the relative efficiency (RE) of equal versus unequal cluster sizes when designing CRTs with a limited number of clusters. In this paper, we are interested in the RE of two bias-corrected sandwich estimators of the treatment effect in the Generalized Estimating Equation (GEE) models for CRTs with a small number of clusters. Specifically, we derive the RE of two bias-corrected sandwich estimators for binary, continuous, or count data in CRTs under the assumption of an exchangeable working correlation structure. We consider different scenarios of cluster size distributions and investigate RE performance through simulation studies. We conclude that the number of clusters could be increased by as much as 42% to compensate for efficiency loss due to unequal cluster sizes.