Wearable, Fiber-less, Multi-Channel System for Continuous Wave Functional Near Infrared Spectroscopy Based on Silicon Photomultipliers Detectors and Lock-In Amplification.

Development and in-vivo validation of a Continuous Wave (CW) functional Near Infrared Spectroscopy (fNIRS) system is presented. The system is wearable, fiber-less, multi-channel (16×16, 256 channels) and expandable and it relies on silicon photomultipliers (SiPMs) for light detection. SiPMs are inexpensive, low voltage and resilient semiconductor light detectors, whose performances are analogous to photomultiplier tubes (PMTs). The advantage of SiPMs with respect to PMTs is that they allow direct contact with the scalp and avoidance of optical fibers. In fact, the coupling of SiPMs and light emitting diodes (LEDs) allows the transfer of the analog signals to and from the scalp through thin electric cables that greatly increase the system flexibility. Moreover, the optical probes, mechanically resembling electroencephalographic electrodes, are robust against motion artifacts. In order to increase the signal-to-noise-ratio (SNR) of the fNIRS acquisition and to decrease ambient noise contamination, a digital lock-in technique was implemented through LEDs modulation and SiPMs signal processing chain. In-vivo validation proved the system capabilities of detecting functional brain activity in the sensorimotor cortices. When compared to other state-of-the-art wearable fNIRS systems, the single photon sensitivity and dynamic range of SiPMs can exploit the long and variable interoptode distances needed for estimation of brain functional hemodynamics using CW-fNIRS.

Estimation of screening sensitivity and sojourn time from an organized screening program.

Regular screening with mammography is widely recommended to reduce breast cancer mortality. However, whether breast screening does more harm than good has long been debated. Since a full evaluation of the effect on mortality could take 10-15 years in order to provide a reliable estimate of the eventual benefits and harms, it is unrealistic to expect each new modification of a screening technique to be evaluated in this way. Therefore, one needs to rapidly estimate suitable measures of the screening effect. In this paper, two measures of interest, the length of the pre-clinical state and the screening false negative rate, are discussed. A procedure is proposed to model the pre-clinical disease state duration, the false negative rate of the screening exam, and the underlying incidence rate in the screened population. We applied the model to data from the Ontario Breast Screening Program in Canada. Our results suggest that the mean preclinical duration is longer than 2 years. We also find only small marginal gains by screening every two instead of three years. The most important objective of a screening program should be to encourage first-time screening attendance.

Breast screening outcomes in women with and without a family history of breast and/or ovarian cancer.

OBJECTIVES: To compare breast screening outcomes between women with a moderate or strong family history of breast and/or ovarian cancer with those without such a history. SETTING: The Ontario Breast Screening Programme (OBSP) is a population-based programme offering mammography and clinical breast examination to Ontario women of 50 and older. METHODS: Data from a cohort of 143,574 women screened by the OBSP from 1996 to 1997 were included. Referral rates, cancer detection rates, positive predictive values and the histological features of screen-detected cancers were examined within family history groups, age groups and screening modalities. Logistic regression analysis of cancer detection was conducted to adjust for potential confounding variables; subgroup analysis by hormone replacement therapy (HRT) use was also undertaken. RESULTS: Compared with women with no family history, women with a moderate or strong family history of breast and/or ovarian cancer were more likely to have their cancer detected (odds ratio [OR]=1.44, 95% confidence interval [CI] 1.20-1.74 and OR=1.42, 95% CI 1.10-1.83, respectively). Among women using HRT, however, there was no association observed between family history and cancer detection (moderate: OR=0.98, 95% CI 0.65-1.48; strong: OR=1.17, 95% CI 0.68-2.02) with history. The histological features of invasive tumours were similar among family history groups. CONCLUSIONS: Greater cancer detection rates and high proportions of invasive tumours with good prognosis indicate that women aged 50 and over with a family history may have the potential to benefit from regular breast cancer screening. Further studies are required to identify optimal screening guidelines and to examine whether HRT reduces the ability to detect cancer in these women.

Socioeconomic status & returning for a second screen in the Ontario breast screening program.

In a retrospective cohort study involving 57902 women initially screened between January 1, 1995 and December 31 1997 by the Ontario Breast Screening Program (OBSP), we examined the relationship between geographically derived socioeconomic status (SES) and returning for a second screen. We controlled for age, rurality, preferred language, initial mammography results, previous mammography history, and referral by a health professional. Although SES was related to returning, rurality was an effect modifier of this relationship, a finding not previously reported. Compared to women in the highest ('richest') quintile, urban women in the first and second quintile were less likely to return; this relationship was not found in rural women. Low SES women, particularly in urban areas, should be specifically targeted to increase their likelihood of re-attendance for breast cancer screening within an organized program.

False-positive result and reattendance in the Ontario Breast Screening Program.

OBJECTIVE: To determine the association between initial screen result and returning for a second screen in an organised breast screening programme for women with a biennial screening recommendation. SETTING: Women who attended the Ontario Breast Screening Program (OBSP). METHODS: A retrospective cohort study was conducted of 140723 Ontario women aged 50 years and older who had an initial screen at the OBSP between 1 July 1990 and 31 December 1995 and were followed until 30 June 1998. Rescreening rates at 36 months and risk ratio estimates were calculated using survival methods. Age of women, year of screen, region (within Ontario) and initial screen result were compared. For initial screen results, returning for a second screen was examined by integration of screening centre with an assessment programme and by modality of referral. RESULTS: Women with a false-positive result were less likely to return for a second screen as were women aged 70 and older and those living in regions of Ontario with fewer OBSP screening centres. However, there were minimal differences in reattendance behaviour by initial screen result for women screened at the OBSP centre with an assessment programme. CONCLUSIONS: Integration of breast screening and assessment services improved reattendance of women with false-positive screen results within an organised screening programme.

Pregnancy outcomes in females after treatment for childhood cancer.

This Ontario province-wide cohort study was conducted to compare the risk of adverse pregnancy outcomes in female childhood cancer survivors who received abdominal-pelvic radiation and/or chemotherapy with alkylating agents with the risk among those who were treated by non-sterilizing alkylating agents with the risk among those who were treated by non-sterilizing surgery only. Females in Ontario, Canada, diagnosed in 1964-1988 before age 20 with a histologically confirmed malignancy and who had survived for at least 5 years, attained age 18, and were alive at the time of study, were identified through the Ontario Cancer Registry. We ascertained pregnancy outcomes by a telephone-administered questionnaire. Treatment data were abstracted from medical records for 830 subjects 18-49 years of age, the analysis comprised 340 survivors who had one or more pregnancies after treatment. There was no evidence of an increased risk of having a spontaneous abortion or an infant with a birth defect. Survivors receiving abdominal-pelvic radiation were more likely to have a low birth weight infant (odds ratio estimate [OR] = 3.64; 95% confidence interval [CI] = 1.33-9.96), a premature low birth weight infant (OR = 3.29; 95% CI = 0.97-11.1), or an infant who died in the perinatal period (OR = 2.41; 95% CI = 0.50-11.5), compared with those receiving surgery. Risks of perinatal death and having a low birth weight infant increased with dose of radiotherapy directed to the abdomen.

Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964-1988 in Ontario, Canada.

This study was conducted to determine the risk of menopause and infertility in female childhood cancer survivors who received abdominal-pelvic radiation and/or chemotherapy with alkylating agents in comparison with those who were treated by nonsterilizing surgery only. Females who were diagnosed in 1964-1988 before age 20 years with a histologically confirmed malignancy and who had survived for at least 5 years, had attained age 18, and were alive at time of study were identified through the Ontario Cancer Registry. Reproductive outcomes were ascertained by a telephone-administered questionnaire, and treatment data were abstracted from medical records for 830 subjects aged 18-49 years; 719 survivors who were nonmenopausal at the end of treatment were included in the analyses. Survivors who received both alkylating agents and abdominal-pelvic radiation were more likely to be postmenopausal than were those who underwent surgery (risk ratio = 2.58; 95% confidence interval: 1.14, 5.80). Women treated with abdominal-pelvic radiation alone had a fertility deficit of 23% compared with those in the surgery group; the deficit was restricted to women diagnosed postpuberty. Risks of menopause and infertility increased with increasing dose of abdominal-pelvic radiation and amount of alkylating agent.

An exploratory case-control study of brain tumors in children.

An exploratory case-control study of childhood brain tumors was conducted in southern Ontario between 1977 and 1983, on 74 cases and 138 age- and sex-matched population controls. A significantly elevated risk (perhaps due to early case symptoms) was seen for skull X-rays at least 5 years prior to diagnosis, and for head or neck injuries which required medical attention. However, no evidence of an increased risk appeared for exposure to sick pets or to pesticides, maternal or paternal history of smoking, and various birth characteristics or antenatal exposure of the child, though these have previously been reported to be associated with childhood brain tumors. With respect to the hypothesis that N-nitroso compounds may be involved in the etiology of childhood brain tumors, most exposures of this type were not associated with risk, though a significant positive association was seen for consumption of beer by the mother during pregnancy, and a significant negative association was seen with consumption of fruit juice by the child. Other findings in the present study include an association with developmental problems relating to height and weight and with certain socioeconomic characteristics of the mother. Further investigation of these results in future studies is warranted.

Components and modifiers of the healthy worker effect: evidence from three occupational cohorts and implications for industrial compensation.

The authors examined the components and modifiers of the healthy worker effect using mortality data from three occupational cohorts: the employees of Atomic Energy of Canada Limited followed between 1950 and 1981, a 10% sample of the Canadian labor force followed between 1965 and 1979, and workers at the Eldorado Resources Limited Beaverlodge uranium mine followed between 1950 and 1980. Two important components of the healthy worker effect have been identified in these cohorts, namely, initial selection of and continuing employment of healthy individuals. There is less evidence for a contribution from the existence of differential risk factors among employed individuals as compared with the general population. The healthy worker effect is, however, substantially modified by time since employment, sex, age, specific cause of death, and specific occupation. Because of this variation, it is inappropriate to account for the healthy worker effect by a single parameter, and all of the above factors must be taken into account in any appropriate analysis. When the only available comparison group for an occupational cohort is the general population, the healthy worker effect is unlikely to have any substantial influence on the process of assessing causality for any observed association or attributing cause in an individual case. This would be particularly true for cancer, and even more so for lung cancer, a disease often associated with industrial compensation cases.

Methodological issues in cohort studies. II: Power calculations.

A simple model is described for estimating power in cohort studies, in which the exposure is treated as a polytomous variable, with a known distribution in the population from which the sample is drawn. The model then requires the specification of the expected number of deaths which will occur in the cohort, calculated from the population rates, the dose-response relationship, and the size of the cohort. The model also allows for misclassification of exposure, the rule rather than the exception in epidemiological studies. The model is applied to a proposed study of saturated fat intake and risk of death from colorectal cancer in a male cohort drawn from the general population. It is demonstrated that this approach leads to an optimization of the power estimates, and in particular that maximization of power can be achieved by using a relatively small number of categories, eg four. It is also demonstrated that the effect of misclassification is less extreme if a polytomous dose-response model is used for analysis as compared to the usual simple dichotomous exposure model.