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Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for highrisk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. ' 2008 Wiley-Liss, Inc.Key words: HPV-DNA testing; cervical screening; HPV test guidelines; HPV test requirements; HPV test statistics It is now well-established and widely, if not universally, accepted that virtually all cervical cancer and its immediate precancerous lesions arise from persisting cervical infections by $15 cancer-associated (high-risk or hr) human papillomavirus (hrHPV) genotypes.1,2 The most important of these HPV genotypes are HPV16 and HPV18, which account for $70% of all invasive cervical cancers with minor variations in this percentage between continents.3 A new paradigm of cervical carcinogenesis replaces an older model of stepwise progression from low-grade to highgrade morphological changes and can now be summarized as four reliably measured stages: (i) HPV acquisition, (ii) HPV persistence (vs. clearance), (iii) progression of a persisting infection to cervical precancer (with incidental co-occurrence of both conditions) and (iv) invasion. 4,5 On the basis of this nearly absolute etiologic link between carcinogenic HPV and cervical cancer, testing for hrHPV is now being considered as an alternative for cytology-based cervical cancer screening. However, before cost-effective implementation of population-based hrHPV testing in cervical cancer screening and prevention can be envisaged, any candidate HPV testing technologies must offer an optimal balance between clinical sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 2 or 3 and treatable cancer (!CIN 2) to minimize redundant or excessive follow-up procedures. Reliable clinical performance needs to be established before any candidate screening test is widely disseminated and adopted into cl...

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Major depressive disorder (MDD) is characterized by high negative affect (NA) and low positive affect (PA), but little is known about emotional reactivity in daily life. The authors used experience sampling methodology to investigate changes in NA and PA following minor daily events in MDD compared with healthy participants. Contrary to expectation, MDD participants did not report more frequent negative events, although they did report fewer positive events. Multilevel regression showed that both NA and PA responses to negative events were blunted in the MDD group, whereas responses to positive events were enhanced. NA responses to negative events persisted longer in MDD participants. Depressed participants with a positive family history or longer current episodes showed relatively greater NA responses to negative events.

Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcome.

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer’s disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2–20.3)/1000 person-years (AD: 11.5 [9.6–13.7], non-AD: 6.1 [4.7–7.7]), compared with 14.2 (11.3–17.6) in controls (AD: 10.1 [7.7–13.0], non-AD: 4.1 [2.6–6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1–1.1]), lower Mini-Mental State Examination (0.7 [0.66–0.8]), and apolipoprotein E ε4 (1.8 [1.3–2.5]) increased the risk of dementia. Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.