DeepFocus: fast focus and astigmatism correction for electron microscopy.

High-throughput 2D and 3D scanning electron microscopy, which relies on automation and dependable control algorithms, requires high image quality with minimal human intervention. Classical focus and astigmatism correction algorithms attempt to explicitly model image formation and subsequently aberration correction. Such models often require parameter adjustments by experts when deployed to new microscopes, challenging samples, or imaging conditions to prevent unstable convergence, making them hard to use in practice or unreliable. Here, we introduce DeepFocus, a purely data-driven method for aberration correction in scanning electron microscopy. DeepFocus works under very low signal-to-noise ratio conditions, reduces processing times by more than an order of magnitude compared to the state-of-the-art method, rapidly converges within a large aberration range, and is easily recalibrated to different microscopes or challenging samples.

Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression.

BACKGROUND: TACE/ADAM17 is a transmembranous protease that cleaves membrane-bound growth factors like EGFR ligands. TACE-dependent proteolysis is regulated by its inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP3). This study analyses the role of TACE and TIMP3 mRNA expression in squamous cell carcinomas of the head and neck (HNSCCs). METHODS: We analysed TACE and TIMP3 mRNA expression in HNSCCs from 106 patients by RNA in situ hybridisation. RESULTS: TACE mRNA was upregulated in HNSCCs compared with dysplastic (P<0.05) and normal epithelia (P<0.001), with strong hybridisation signals in 21.9% of invasive tumour tissues and 4.5% of dysplasia. Elevated mRNA levels were accompanied by increased amounts of TACE protein in HNSCCs. TIMP3 mRNA expression in HNSCC-associated stroma was significantly higher than in the stroma adjacent to dysplastic or normal epithelia. Expression of TACE mRNA in HNSCCs was associated with tumour stage (P=0.019) and regional lymph node metastasis (P=0.009). Furthermore, levels of TACE mRNA in HNSCCs correlated with the expression of TIMP3 mRNA in HNSCC-associated stroma. Concomitantly, patients expressing high levels of TACE and TIMP3 mRNA showed significantly reduced overall survival compared with those with low mRNA levels. CONCLUSION: Our results indicate an important role of TACE and TIMP3 during development and progression of HNSCCs.

Perceptions of HPV and cervical cancer among Haitian immigrant women: implications for vaccine acceptability.

INTRODUCTION: Women in Haiti and throughout the Haitian Diaspora shoulder a disproportionate burden of cervical cancer morbidity and mortality. The widespread Human Papillomavirus (HPV) vaccination holds promise for helping to attenuate this disparity. However, previous research has not fully examined Haitian women's perceptions of, and barriers to, HPV vaccination, which is essential for informing future intervention. The current paper aims to fill this gap. METHODS: As part of ongoing Community-Based Participatory Research (CBPR) efforts, we conducted a series of focus groups with Haitian immigrant women in Little Haiti, the predominantly Haitian neighborhood in Miami, Florida, U.S. Focus group questions assessed women's knowledge and beliefs about cervical cancer and HPV, their opinions of vaccines in general, their knowledge and perceptions of the HPV vaccine specifically and health communications preferences for cervical cancer prevention. RESULTS: Among the participants who had heard of HPV, many held misconceptions about virus transmission and did not understand the role of HPV in the development of cervical cancer. Virtually all participants expressed support for vaccines in general as beneficial for health. Some women had heard of the HPV vaccine, primarily as the result of a contemporary popular media campaign promoting the Gardasil® vaccine. Physician recommendation was commonly mentioned as a reason for vaccination, in addition to having more than one sex partner. Women felt the HPV vaccine was less appropriate for adolescent girls who are presumed as not sexually active. Women indicated a strong preference to obtain health information through trusted sources, such as Haitian physicians, Haitian Community Health Workers, and especially Kreyol-language audiovisual media. DISCUSSION: Study findings indicate a need for culturally and linguistically appropriate educational initiatives to promote awareness of HPV and its role in cervical cancer, the importance of vaccination against the virus, explicitly differentiating HPV from HIV and providing specific information about vaccine safety. CONCLUSION: In the U.S., there is a substantial lack of educational information available in Haitian about HPV and cervical cancer. This gap results in missed opportunities to promote disease prevention through vaccination and regular screening. Addressing such gaps is essential for achieving health equity among Haitian immigrant women and other, similarly underserved women, who are disproportionately burdened by cervical cancer.

Intrinsic Capacitiy Monitoring by Digital Biomarkers in Integrated Care for Older People (ICOPE).

The WHO action plan on aging expects to change current clinical practices by promoting a more personalized model of medicine. To widely promote this initiative and achieve this goal, healthcare professionals need innovative monitoring tools. Use of conventional biomarkers (clinical, biological or imaging) provides a health status assessment at a given time once a capacity has declined. As a complement, continuous monitoring thanks to digital biomarkers makes it possible to remotely collect and analyze real life, ecologically valid, and continuous health related data. A seamless assessment of the patient's health status potentially enables early diagnosis of IC decline (e.g. sub-clinical or transient events not detectable by episodic evaluations) and investigation of its probable causes. This narrative review aims to develop the concept of digital biomarkers and its implementation in IC monitoring.

Novobiocin modulates colchicine sensitivity in parental and multidrug-resistant B16 melanoma cells.

The effect of the antibiotic agent novobiocin on the sensitivity of melanoma cells to colchicine and vinblastine was examined in drug-sensitive and drug-resistant B16 melanoma cells. A cell line COL/R was selected for colchicine resistance. The COL/R cell line (resistant to 80 ng/ml colchicine) was found to possess the multidrug-resistant (MDR) phenotype. The cells were shown to be cross-resistant to vinblastine and Adriamycin and to overexpress P glycoprotein. P glycoprotein activity was assessed by using the rhodamine 123 accumulation test. Rhodamine accumulation was markedly decreased in COL/R cells as compared to the parental B16 cells. Verapamil reversed drug resistance and increased rhodamine accumulation in COL/R cells. Novobiocin in combination with colchicine or vinblastine synergistically inhibited the proliferation of parental B16 cells. In COL/R cells, novobiocin markedly decreased colchicine resistance and increased rhodamine accumulation. These data show that novobiocin increases the sensitivity of both parental and MDR melanoma cells to microtubule-disrupting cytotoxic drugs.

Investigation of a reported cluster of bladder cancer cases in the Pottstown/Phoenixville area of Pennsylvania.

A urologist in Phoenixville, Pennsylvania, noted an apparent excess of invasive bladder cancer cases in his practice area during 1988 and 1989. Background incidence data for the local area were derived from state Cancer Registry statistics. Seventeen additional cases were noted during review of local hospital tumor registry data. Exposure evaluation included complete occupational histories for 15 index cases and correlation of residential histories with a review of local industries, water quality data, and toxic waste sites. The data were compared with incidence data from 1984 and 1985, and no increase in bladder cancer incidence for this area in 1988 and 1989 was evident. There was, however, a higher bladder cancer incidence among white males in the study area and Chester County, compared with Pennsylvania as a whole. Residential histories and environmental analysis did not reveal a common environmental carcinogen. A high incidence of occupational exposure to suspected bladder carcinogens was noted. In addition, all but 4 of the index cases smoked cigarettes. The study was limited by an extreme paucity of water supply analysis data. Effective environmental monitoring would promote more effective research into environmental carcinogenesis.

Building effective partnerships: a national evaluation of the Cancer Information Service outreach program. Part 2.

The Cancer Information Service's (CIS) nationally coordinated, regionally focused outreach program establishes partnerships with government, nonprofit, and private organizations to reach underserved and minority populations. A national random sample telephone survey, conducted with 867 partner organizations who had contact with the CIS in early 1996, assessed the types of CIS assistance used, satisfaction with and usefulness of these services, organizational characteristics, and the overall impact on partners' cancer-related programs. CIS partners provide programs for the medically underserved (79%) and specific racial and ethnic groups (72%) and address a range of cancer control issues. Partners use and highly value an array of CIS assistance. Over 90% are satisfied with the CIS services. Diffusion of accurate and science-based information, materials and resources is a key element of the outreach assistance. Two out of three partners are receiving late-breaking news and scientific information from the CIS and 86% are disseminating it to their constituents. The majority of those partners surveyed reported that they rely on the CIS to assist with their most important cancer programs. Sixty-eight percent of the partners rated the CIS assistance as important or very important to their cancer-related programs. These survey results indicate that the CIS outreach program provides key support to partners' cancer programs and has an impact on their efforts. The results support the effectiveness of a regionally based outreach program working in partnership with existing organizations at the state, county, and local level who are addressing the needs of underserved populations.

Reaching minority and underserved populations: the impact of the Cancer Information Service's outreach program. Part 3.

Through its regional outreach program, the Cancer Information Service (CIS) develops partnership with organizations that reach minority and underserved populations and connects them with accurate cancer information and an array of support services and resources. To evaluate the usefulness, satisfaction, and impact of the CIS outreach program on partner organizations, a national random sample survey was conducted by an independent research firm in 1996. This paper focuses on the survey results of 359 special population partner organizations that identified their main audience as a specific racial or ethnic group and/or the underserved. Almost all (84% to 93%) rated the services provided by the CIS outreach program to be very important or important to meeting the goals of their projects. A large majority of these special population partners stated that the CIS provided them with the latest cancer information (67%) and National Cancer Institute (NCI) resources (83%), and more than half (57%) utilized CIS expertise to develop and plan programs. Special populations partners were more likely to use an array of CIS assistance than other CIS partners. Furthermore, they were more likely to be heavy users of CIS assistance and more likely than other CIS partners to indicate that the CIS had an important impact on their programs. The results indicate that the CIS's nationally coordinated, regionally focused outreach program provides critical support and has an important impact on the cancer-related programs of partner organizations that reach minority and underserved audiences.

Cumulative exposure to inorganic lead and neurobehavioural test performance in adults: an epidemiological review.

OBJECTIVES: To evaluate the current evidence that cumulative exposure to inorganic lead is associated with decreased performance in neurobehavioural tests in adults. METHODS: 21 unique studies were reviewed from 28 published manuscripts. An algorithm was developed to determine the usefulness of each study on the basis of exposure assessment, control of confounding variables, methods of subject selection, test conditions, and data analysis. Highest emphasis was placed on the use of cumulative measures of exposure or absorption. RESULTS: Only three studies used a measure of cumulative exposure to or absorption of lead, and two others used duration of exposure as a surrogate for cumulative exposure. All other studies used a measure that did not adequately estimate cumulative exposure to lead, most often current blood lead concentration. 20 of the studies controlled for age as a confounding variable, although in several studies the possibility for residual confounding by age remained. 16 studies controlled for intellectual ability before exposure; all of them used educational level for this purpose. Of the five studies that used direct or surrogate measures of cumulative exposure to or absorption of lead, two were thought to be of low usefulness because of inadequate duration of exposure. The three remaining studies found stronger associations of neurobehavioural performance with recent exposure measures than with those of cumulative exposure. CONCLUSION: The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioural tests in adults. The current evidence is flawed because of inadequate estimation of cumulative exposure to or absorption of lead and inadequate control for age and intellectual ability before exposure.

[Changes in the ST segment in unstable angina pectoris. Its prognostic value]. / Alteraciones del segmento ST en la angina pectoris inestable. Su valor pronóstico.

Out of 145 patients with unstable angina hospitalized at CCU of the Instituto de Cardiologia do Rio Grande do Sul (Brazil) in 1981, 69 were studied: group I = 23 case (33.3%) with transient ST segment depression, group II = 13 cases (18.8%) with transient ST segment elevation, group III (control) = 33 cases (47.8%) without acute EKG changes. Group I showed a higher incidence of double-triple coronary artery involvement: 71.4% VS 53.8 and 63.3% respectively (non significant). This group also showed a higher number of patients with severe angina and who suffered acute myocardial infarction during follow-up, although without statistical significance. There were 8 deaths (34.8%) in group I, 3 (23.1%) in group II and 4 (12.1%) in group III (chi 2 = 4.11, p greater than 0.05). The 36 months survival rate was lower in group I than in groups II and III: 52.9% VS. 75.2% (NS) and 89.7% (P less than 0.02) respectively. We conclude that acute EKG changes, mainly transient ST segment depression, in unstable angina, are markers of high risk patients.