Childhood tonsillectomy alters the primary distribution of HPV‐related oropharyngeal squamous cell carcinoma

ObjectivesWe investigated how tonsillectomy during childhood may influence the distribution of human papillomavirus (HPV) positive cancer of the tonsils in adult life using p16 as a surrogate marker for HPV infection.Study DesignRetrospective observational study.MethodsA total of 280 patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) and known p16 status were eligible for this study. Each participant was called to obtain the childhood tonsillectomy history. Respondents were subgrouped by p16 status and the primary tumor location. Patient demographic and clinical information was analyzed for association with Fisher’s exact and Wilcoxon rank sum tests. Location of tumor was modeled using univariate (UVA) and multivariate (MVA) logistic regression with associated odds ratios (OR) and 95% confidence intervals.ResultsOf the 280 patients, 115 (41%) were respondents: 104 (90.4%) were p16 positive and 11 (9.6%) were p16 negative. For p16 positive patients, we observed a majority (93%) of intact tonsils in those with tonsil cancer, compared to 45% of intact tonsils in patients with p16 positive cancer elsewhere in the oropharynx (P < .001). MVA logistic regression showed that female gender (OR = 4.16, P = .0675), prior smoking history (OR = 2.6, P = .0367), and intact tonsils (OR = 15.2, P < .0001) were associated with tonsillar OPSCC.ConclusionWe found that patients with p16 positive OPSCC at a non‐tonsil site were much more likely to have had prior tonsillectomy vs those with p16 positive OPSCC arising within the tonsil. Nevertheless, we do not advocate tonsillectomies as a public health policy to reduce HPV‐related OPSCC.Level of Evidence6Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154902/1/lio2342_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154902/2/lio2342.pd

Skin cancer screening participation and impact on melanoma incidence in Germany – an observational study on incidence trends in regions with and without population-based screening

Background: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003–June 2004), but not in the German state of Saarland. Methods: The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. Results: Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100 000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100 000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: −10.6 per 100 000 (95% CI: −13.3; −7.9); men: −4.1 per 100 000 (95% CI: −6.5; −1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. Conclusion: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers

Predictors of dropout in the German disease management program for type 2 diabetes

Background: To improve and assess the effectiveness of disease management programs (DMPs), it is critical to understand how many people drop out of disease management programs and why. Methods: We used routine data provided by a statutory health insurance fund from the regions North Rhine, North Wurttemberg and Hesse. As part of the German DMP for type 2 diabetes, the insurance fund received regular documentation of all members participating in the program. We followed 10,989 patients who enrolled in the DMP between July 2004 and December 2005 until the end of 2007 to study how many patients dropped out of the program. Dropout was defined based on the discontinuation of program documentation on a particular patient, excluding situations in which the patient died or left the insurance fund. Predictors of dropout, assessed at the time of program enrolment, were explored using logistic regression analysis. Results: 5.5% of the patients dropped out of the disease management program within the observation period. Predictors of dropout at the time of enrolment were: region; retirement status; the number of secondary diseases; presence of a disabling secondary disease; doctors recommendations to stop smoking or to seek nutritional counselling; and the completion and outcome of the routine foot and eye exams. Different trends of dropout were observed among retired and employed patients: retired patients of old age, who possibly drop out of the program due to other health care priorities and employed people of younger age who have not yet developed many secondary diseases, but were recommended to change their lifestyle. Conclusions: Overall, dropout rates for the German disease management programs for type 2 diabetes were low compared to other studies. Factors assessed at the time of program enrolment were predictive of later dropout and should be further studied to provide information for future program improvements

Co-Crystal Structures of PKG Iβ (92–227) with cGMP and cAMP Reveal the Molecular Details of Cyclic-Nucleotide Binding

Cyclic GMP-dependent protein kinases (PKGs) are central mediators of the NO-cGMP signaling pathway and phosphorylate downstream substrates that are crucial for regulating smooth muscle tone, platelet activation, nociception and memory formation. As one of the main receptors for cGMP, PKGs mediate most of the effects of cGMP elevating drugs, such as nitric oxide-releasing agents and phosphodiesterase inhibitors which are used for the treatment of angina pectoris and erectile dysfunction, respectively. configuration, with a conserved threonine residue anchoring both cyclic phosphate and guanine moieties. The structure of CNBD-A in the absence of bound cyclic nucleotide was similar to that of the cyclic nucleotide bound structures. Surprisingly, isothermal titration calorimetry experiments demonstrated that CNBD-A binds both cGMP and cAMP with a relatively high affinity, showing an approximately two-fold preference for cGMP. conformation through its interaction with Thr193 and an unusual cis-peptide forming residues Leu172 and Cys173. Although these studies provide the first structural insights into cyclic nucleotide binding to PKG, our ITC results show only a two-fold preference for cGMP, indicating that other domains are required for the previously reported cyclic nucleotide selectivity

Aktivierung heterolog exprimierter α\alpha-Untereinheiten zyklisch-Nukleotid gesteuerter Ionenkanäle durch Agonisten

Bei Beginn der Arbeit (November 1989) war das erste Mitglied der Familie der CNG Kanale kloniert. Durch heterologe Expression in Xenopus Oozyten war bewiesen, daß das klonierte Protein bezüglich seiner Empfindlichkeit für cGMP und seines Einzelkanalleitwerts wit den Eigenschaften des in situ gemessenen Kanals übereinstimmt (Kaupp et al., 1989), als Übersicht über die Eigenschaften des in situ gemessenen Kanals von unterschiedlichen Spezies siehe Yau & Baylor, 1989.Alle in dieser Arbeit gezeigten Daten stammen von CNG-Kanal $\alpha$-Untereinheiten, die in Xenopus Oozyten exprimiert wurden. Das Oozytenexpressionssystem bietet im Vergleich zum nativen Kanal wichtige Vorteile: Das exprimierte Protein ist zugänglich für gezielte Mutationen, und es kann isoliert von der biochemischen Kaskade untersucht werden, die die Eigenschaften in situ moduliert

Adapt or Perish: Algebra and Visual Notation for Service Interface Adaptation

The proliferation of services on the web is leading to the formation of service ecosystems wherein services interact with one another in ways not necessarily foreseen during their development or deployment. A key challenge in this setting is service mediation: the act of retrofitting existing services by intercepting, storing, transforming, and (re-)routing messages going into and out of these services so they can interact in unforeseen manners. This paper addresses a sub-problem of service mediation, namely service interface adaptation, that arises when the interface that a service provides does not match the interface that it is expected to provide in a given interaction. The paper focuses on reconciling mismatches between behavioural interfaces, i.e. interfaces that capture ordering constraints between interactions. It presents a declarative approach to service interface adaptation based on: (i) an algebra over behavioural interfaces; and (ii) a visual language that allows pairs of provided-required interfaces to be linked through algebraic expressions. These expressions are fed into an execution engine that intercepts, buffers, transforms and forwards messages to enact the adaptation logic