Significance test of clustering under high dimensional setting with applications to cancer data

For high dimensional data, the SigClust is developed for testing the significance of clustering. The cluster index (CI) for SigClust is conducted by the ratio of the within-cluster and total sum of squares. But its empirical size is too conservative to be over controlled. By removing the cumbrous terms in the CI, an improved index (BCI) is proposed in this paper. The coefficient of variation of the BCI can be significantly reduced, implying that the new index BCI is stable. Moreover, the new significance test (NewSig) maintains the size, meanwhile, provides a greater power. Simulation experiments and two real cancer data examples are analysed for illustrating the performance of the new methodology.     

Human papillomavirus vaccine and Pap tests on college campuses: How do historically black colleges and universities (HBCUs) measure up?

ABSTRACT

Objective: The availability of cervical cancer prevention services at college health centers was compared between historically black colleges and universities (HBCUs) and non-HBCUs.

Methods: Four-year, non–primarily distant learning colleges, matching HBCUs with randomly selected non-HBCUs within the same states (N = 136) were examined. Data were collected (2014–2015 academic year) on the availability of human papillomavirus (HPV) vaccine and Pap tests at college health centers. HBCUs were compared with non-HBCUs using conditional logistic regression, and correlates of offering these services were identified. Results: Many institutions did not offer HPV vaccine or Pap tests. Fewer HBCUs offered HPV vaccine (18% vs 53%) and Pap tests (50% vs 76%) compared with non-HBCUs. In multivariable analyses, HBCUs remained less likely than non-HBCUs to offer HPV vaccine (odds ratio [OR] = 0.07, 95% confidence interval [CI]: 0.02–0.26) and Pap tests (OR = 0.19, 95% CI: 0.06–0.61). Conclusions: Greater effort is needed to make cervical cancer prevention services available at colleges, especially at HBCUs.     

Indoor Tanning and Problem Behavior

Objective: The authors examined factors predicting college students' use of tanning beds. Participants and Methods: Undergraduate students (N = 745) at a large Northeastern university participated in the study by answering a survey measuring tanning behavior and other psychosocial variables, including sensation seeking, self-esteem, tanning image beliefs, and friends' tanning bed use. Results: All 3 systems from problem behavior theory predicted past tanning bed use and intention to use tanning beds. The authors observed a positive association between sensation seeking and intention to use tanning beds. Tanning image beliefs were positively associated with both past tanning behavior and intention to use tanning beds. Conclusions: Interventions focusing on friend and acquaintance social network influences may be more effective than health-risk campaigns in reducing tanning bed use.     

The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer

Objective.?To evaluate body composition changes, specifically skeletal muscle mass, in men receiving androgen deprivation with luteinizing-hormone releasing hormone-agonist (LHRH-A) for prostate cancer (PCa) in comparison with healthy controls.

Design.?Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial.

Setting.?Clinical Research Center in Connecticut.

Participants.?Thirty men (> 60 years) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa.

Measurements.?Appendicular skeletal muscle/height² (ASM/ht²), lean and fat mass were assessed by dual energy x-ray absorptiometry. Total testosterone levels were assessed by enzyme immunoassay.

Results.?At baseline, 12/30 (40%) of the treatment group and 7/25 (28%) of the control group (p = 0.11) met criteria for sarcopenia. There were no differences between control groups in ASM/ht² or lean mass. The LHRH-A group had a higher percent body fat than the control group, 29.8 ± 6.3 versus 26.3 ± 4.6 (p = 0.02). ASM/ht² and lean mass decreased in the LHRH-A group from 7.5 ± 0.9 kg to 7.3 ± 0.9 kg (?2.3% ± 0.03; p ? 0.001) and 53.5 ± 5.4 kg to 52.3 ± 5.3 kg (?2.1% ± 0.03; p ? 0.001), respectively. There was no muscle loss in the control group. At 6 months, the LHRH-A group had increased percent body fat from 29.8 ± 6.4 to 32.2 ± 5.8 (9.5% ± 0.13; p ? 0.001), whereas the control group had decreased in percent body fat from 26.6 ± 4.6 to 25.3 ± 5.0 (?3.8% ± 0.08; p = 0.02).

Conclusions.?Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy. Lifestyle changes or medical interventions to minimize the effects of androgen deprivation therapy for PCa deserve investigation.     

The aging male in the 21st century

Background.?Prostate cancer incidence varies significantly among different ethnic groups. However, the report concerning the clinical outcome after radical prostatectomy (RP) in the low incidence Asian population is still limited. We aimed to compare the clinical outcome in patient treated with RP among different ethnic groups and to identify significant prognostic factors in Taiwanese patients.

Methods.?A total of 341 patients with clinical localized prostate cancer undergoing curative RP in three medical centers in Taiwan were included in this study. Ethnic group comparison was performed using the CaPSURE, SEARCH databases from United States (US) and one large European series. The Kaplan–Meier analysis and Cox proportional hazard model were used to identify significant predictors for prostate-specific antigen (PSA) recurrence.

Results.?Compared to the Caucasian white population in the US and Europe studies, the Taiwanese population have higher age at surgery and higher pre-operative PSA level. With mean and median follow-up of 39.1 months and 31.0 months (range 5–120 months), 127 men (37.2%) had PSA recurrence which was significant higher than the Western series. Significant predictors for PSA recurrence identified in the post-operative overall model were PSA level, pathological Gleason Score, pathological tumor stage and lymph node metastasis.

Conclusions.?The clinical outcome of Taiwanese male with prostate cancer post-RP appears inferior to the Western country, which is largely due to delay surgery at higher PSA level. Earlier diagnosis and treatment may improve the cancer control of RP.     

Clinical experiences with testosterone therapy: prostate safety

Due to a decrease in Leydig cell function, a considerable proportion of men over 50 years of age will develop hypogonadism. Consequently, loss of libido and several other testosterone-dependent symptoms may become evident. When decreased levels of biologically available testosterone are found, and corresponding symptoms are present, these men could be eligible for testosterone substitution therapy. Testosterone treatment in testosterone-deprived men has been shown to improve general well-being, osteoporosis, muscle atrophy, libido and - if present - anemia. Despite these positive effects, testosterone treatment has to be performed with caution. Although it has not been proven that elevation of the serum testosterone level to the normal range results in a greater risk of developing prostate cancer, the effects of testosterone on a prostate cancer already present are well established. Several studies have demonstrated that testosterone treatment does not result in a significant increase in serum levels of prostate-specific antigen (PSA) or prostate volume. The long-term effects, however, are currently unknown. For these reasons, testosterone treatment should be performed only when the presence of prostate cancer is unlikely; i.e. when PSA levels are within normal limits and digital rectal examination does not reveal any suspicious findings. These examinations may still miss some small prostate cancers that could be promoted by testosterone treatment. The determination of PSA levels under testosterone treatment is necessary every 3 months, at least for the first year. Steadily rising PSA levels require immediate cessation of testosterone administration and the initiation of further diagnostic procedures (prostate biopsy), to rule out prostate cancer.     

Male breast cancer

Male breast cancer (MBC) is a rare disease. However, as global populace ages, there is a trend to MBC increasing. Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. Clinic manifestation is painless hard and fixed nodule in the subareolar region in 75% of cases, with nipple commitment earlier than in women. Breast cancer has similar prognostic factors in males and females, among which axillary adenopathy (present in 40–55% cases) is the most important one. Although mammography, ultrasonography and scintigraphy can be useful tools in diagnosis; clinical assessment, along with a confirmatory biopsy, remains the main step in the evaluation of men with breast lesions. Infiltrating ductal carcinoma is the most frequent histological type. The established standard of care is modified radical mastectomy followed by tamoxifen for endocrine-responsive positive disease, although other options are being explored. While similarities between breast cancer in males and females exist, it is not appropriate to extrapolate data from female disease to the treatment of male. There is a need for specific multi-institutional trials to better understanding of clinicopathologic features and establishment of optimal therapy for this disease.     

Group Work as a Protective Factor for Immigrant Youth

While constructing a cultural understanding of the adaptation process of Hispanic immigrant youth, this article illustrates how social group process acts as a "protective factor" which promotes a capacity for competence and mastery over their new environment.     

Commentary: Flawed Scientific-Evidence Standards Delay Diesel Regulations

Of 188 government-monitored air toxics, diesel particulate matter (DPM) causes seven times more cancer than all the other 187 air toxics combined, including benzene, lead, and mercury. Yet, DPM is the only air toxic not regulated more stringently under the Clean Air Act, as a hazardous air pollutant (HAP). One reason is that regulators use flawed standards of scientific evidence. The article argues (1) that DPM meets all six specified evidentiary criteria, any one of which is sufficient for HAP regulation and (2) that regulators’ standards of evidence for denying HAP status to DPM (no DPM unit-risk estimate, inadequate dose-response data, alleged weak mechanistic data) err logically and scientifically, set the evidence bar too high, delay regulation, and allow 21,000 avoidable DPM deaths annually in the U.S.     

A pragmatic adaptive enrichment design for selecting the right target population for cancer immunotherapies

One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more prespecified biomarker subpopulations at an interim analysis have been proposed in this setting but practical case studies of AEDs are still relatively rare. We present the design of an AED with a binary endpoint in the highly dynamic setting of cancer immunotherapy. The trial was initiated as a conventional trial in early triple-negative breast cancer but amended to an AED based on emerging data external to the trial suggesting that PD-L1 status could be a predictive biomarker. Operating characteristics are discussed including the concept of a minimal detectable difference, that is, the smallest observed treatment effect that would lead to a statistically significant result in at least one of the target populations at the interim or the final analysis, respectively, in the setting of AED.