Genetic progression and the waiting time to cancer

Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies of cancer cells have shown that the mutational landscape of cancer is complex and that individual cancers may evolve through mutations in as many as 20 different cancer-associated genes. We use data published by Sjöblom et al. (2006) to develop a new mathematical model for the somatic evolution of colorectal cancers. We employ the Wright-Fisher process for exploring the basic parameters of this evolutionary process and derive an analytical approximation for the expected waiting time to the cancer phenotype. Our results highlight the relative importance of selection over both the size of the cell population at risk and the mutation rate. The model predicts that the observed genetic diversity of cancer genomes can arise under a normal mutation rate if the average selective advantage per mutation is on the order of 1%. Increased mutation rates due to genetic instability would allow even smaller selective advantages during tumorigenesis. The complexity of cancer progression can be understood as the result of multiple sequential mutations, each of which has a relatively small but positive effect on net cell growth.     

Determinants and effects of waiting time to coitus.

Nonuse of contraception at first intercourse among adolescents is well documented in the adolescent sexuality research literature. This study provides a formal test of the hypothesis that an increase in the courtship period (i.e., waiting time to intercourse) increases the likelihood that a couple will discuss contraception and use it at first intercourse. The data analyzed are from personal interviews with 1,314 women aged 20-29 in the 1983 National Survey of Unmarried Women. The results are mixed about the effect of waiting time on contraceptive behavior, providing weak support for the hypothesis, but also elucidating individual and relative characteristics of the couples, such as age and education of the respective partners, that affected contraceptive behavior at first intercourse. Support for the hypothesis may prove more robust in data with different characteristics from the survey used here.     

Willingness of patients to change surgeons for a shorter waiting time for joint arthroplasty

Background

To improve access to care, many jurisdictions have proposed waiting-time benchmarks and guarantees. We assessed the willingness of patients to consider changing their surgeon to one with a shorter waiting time for arthroplasty.

Methods

We mailed a questionnaire to 2 random samples of patients who either were awaiting hip or knee replacement arthroplasty or had had one of these procedures within the preceding 3–12 months. We used logistic regression to assess the determinants of patients'' likelihood to consider changing surgeons.

Results

Of 1200 responses from a sample of 2000, 557 (46%) were from patients awaiting surgery and 643 (54%) were from people who had undergone surgery. The mean age of respondents was 69.9 years (standard deviation 10.8), and 682 (57%) were women. The median waiting time for surgery was 8 months. Overall, 753 (63%) of the patients were unlikely to consider changing surgeons. Increased likelihood of changing surgeons was associated with male sex (adjusted odds ratio [OR] 1.49, 95% confidence interval [CI] 1.10–2.02), a high school education or higher (OR 1.73, 95% CI 1.15– 2.62) and having already undergone surgery (OR 1.71, 95% CI 1.19– 2.46). Decreased likelihood was associated with preference for a particular surgeon before referral (OR 0.57, 95% CI 0.42– 0.79), a better score on the EuroQol (EQ-5D) index (a measure of health-related quality of life) (OR 0.39, 95% CI 0.24– 0.66), perception that the waiting time to see the surgeon was acceptable (OR 0.50, 95% CI 0.36–0.70), perception that the waiting time to surgery was acceptable (OR 0.62, 95% CI 0.43–0.91) and perceived fairness of treatment (OR 0.53, 95% CI 0.36– 0.78).

Interpretation

Despite long waits for surgery, most patients, if given the choice, would be unlikely to change their surgeon to one with a shorter waiting time.Long waiting times for elective surgery are a concern in countries with publicly funded health care systems.¹ To try to improve access, governments in Canada and some other countries in the Organisation for Economic Co-operation and Development have proposed or implemented waiting-time benchmarks and care guarantees.² These benchmarks, typically between 3 and 12 months, usually refer to the time between assessment by a specialist and in-patient treatment.³Waiting times for hip and knee arthroplasty are perceived as excessive in many countries, including Canada.^4–6 In 2005, Canada''s federal, provincial and territorial health ministers set a target waiting time of 26 weeks for hip and knee arthroplasty, and in 2007 they agreed to establish waiting-time guarantees by 2010 in selected priority areas, including joint arthroplasty.⁷ A waiting-time guarantee implies that, if necessary medical treatment for a publicly insured service is not available within a medically acceptable timeframe, patients may receive treatment at another facility, even outside their home province, at public expense. This change in the location of treatment implies that another surgeon would perform the surgery. However, patients are not always willing to accept re-referral to a provider with a shorter waiting time.^8–12Most other studies investigating patient choice in the context of long waiting times have referred to the choice of an alternative hospital rather than the choice of an alternative surgeon. Even though many patients may indicate that they are willing to travel to another hospital, fewer actually choose such a change.¹¹ In addition to waiting time,^8,13 other factors influencing provider choice are the hospital''s reputation, follow-up care and travel time.^8,13,14 Little is known about what factors patients consider and what information they want and can use when choosing a provider.^11,15We sought to assess patients'' willingness to consider changing to a surgeon with a shorter waiting time for hip and knee arthroplasty. We formulated the following research questions: Would patients consider changing to a surgeon with shorter waiting times? What factors influence patients'' willingness to consider changing surgeons? Do patients waiting for surgery have a different perspective than patients who have already undergone their surgery?     

A study of waiting time in an emergency department

A study was undertaken to determine the time spent by 3459 patients in the Emergency Department of the hospital and also to assess whether full-time physician supervision of interns appreciably influenced this time.The study was divided into three phases, each lasting two weeks. Cases were classified into five graded categories of severity. The data so accumulated were subjected to computer analysis, and time intervals relevant to the study obtained.Mean waiting times compared favourably with those recorded in other studies. Full-time physician supervision of interns was found to produce a small, but none the less appreciable, decrease in this time.     

Dependence of the motor response time in discrimination task on the character of visual information available

The interaction of visual and proprioceptive afferentation were studied in the motor task for discrimination of weights of falling objects. The availability of visual information reduced the time of motor response; however, the degree of shortening depended on the type of this information. The decrease in the response time was significantly greater when the subject saw the beginning of the real falling of object instead of having only visual information about the beginning of the fall. Thus, a subject solves the motor task for discrimination of weights of falling objects more efficiently when he sees the real beginning of the fall, rather than in the case when the subject receives only a visual signal at the moment when an electromagnet releases the object. This may be due to the fact that seeing the initial part of a real trajectory instead of an abstract signal about the beginning of the fall allows the subject to better predict the moment of the impact.     

Concordance between partners in desired waiting time to birth for newlyweds in India

Examining waiting time to birth among newlywed couples is likely to provide insights into the desire for spacing births among newlywed husbands and wives. Data from the Indian National Family Health Survey of 2005-06 are used to examine the desired waiting time (DWT) to birth among newlywed couples. The dependent variable is spousal concordance on desired waiting times. Overall 65% of couples have concordant desired waiting times. Among discordant couples, wives were more likely to want to wait longer than their husbands. Couples from richer wealth quintiles were more likely than couples from the poorest quintile to have concordant desired waiting times. Muslims were less likely than Hindus to have concordant desires. There is a need for spacing contraceptive methods among newlyweds in India. This may have implications for the Indian Family Planning Programme, which to date has largely focused on sterilization. Programmes need to include newlywed husbands to promote use of spacing methods.     

Muscle contraction and relaxation-response time in response to on or off status of visual stimulus

Background

It is unclear whether response time is affected by a stimulus cue, such as a light turned on or off, or if there are differences in response to these cues during a muscle contraction task compared with a muscle relaxation task. The objective of this study was to assess the response time of a relaxation task, including the contraction portion of the task, to a stimulus of a light turned on or off. In addition, we investigated the effect of the pre-contraction level on the relaxation task.

Results

Contraction response time was significantly shorter during the light-on status than during the light-off status (P <0.01), and relaxation response time in each maximum voluntary contraction was significantly longer during the light-on status than during the light-off status (P <0.01). The relaxation response time became longer in order of 25% to 75% maximum voluntary contraction regardless of light-on or -off status, and was significantly longer than the contraction response time (P <0.05-0.01).

Conclusions

This study found that as the contraction level increased, the relaxation response time became longer than the contraction response time regardless of light status. However, contraction response time or relaxation response time findings were opposite to this during the light-on status and light-off status: contraction response time became shorter in the light-on status than in the light-off status and relaxation response time became longer in the light-on status than in the light-off status. These results suggest that the length of each response time is affected by motor control in the higher order brain and involves specific processing in the visual system.     

Determinants of waiting time to third pregnancy using censored linear regression

The intervals between pregnancies have important effects on fertility and maternal and infant health outcomes. This study uses linear regression with censored observation to assess the determinants of the waiting time to third pregnancy. The analysis is applied to data from the Second Malaysian Family Life Survey consisting of 1172 women who had their second delivery ending in a live birth. Contraceptive use, age of the woman, duration of breast-feeding, length of previous pregnancy interval and education of the woman all affect the waiting time to third pregnancy significantly.     

Space and time in visual context

No sensory stimulus is an island unto itself; rather, it can only properly be interpreted in light of the stimuli that surround it in space and time. This can result in entertaining illusions and puzzling results in psychological and neurophysiological experiments. We concentrate on perhaps the best studied test case, namely orientation or tilt, which gives rise to the notorious tilt illusion and the adaptation tilt after-effect. We review the empirical literature and discuss the computational and statistical ideas that are battling to explain these conundrums, and thereby gain favour as more general accounts of cortical processing.     

Unfolding visual lexical decision in time

Visual lexical decision is a classical paradigm in psycholinguistics, and numerous studies have assessed the so-called "lexicality effect" (i.e., better performance with lexical than non-lexical stimuli). Far less is known about the dynamics of choice, because many studies measured overall reaction times, which are not informative about underlying processes. To unfold visual lexical decision in (over) time, we measured participants' hand movements toward one of two item alternatives by recording the streaming x,y coordinates of the computer mouse. Participants categorized four kinds of stimuli as "lexical" or "non-lexical:" high and low frequency words, pseudowords, and letter strings. Spatial attraction toward the opposite category was present for low frequency words and pseudowords. Increasing the ambiguity of the stimuli led to greater movement complexity and trajectory attraction to competitors, whereas no such effect was present for high frequency words and letter strings. Results fit well with dynamic models of perceptual decision-making, which describe the process as a competition between alternatives guided by the continuous accumulation of evidence. More broadly, our results point to a key role of statistical decision theory in studying linguistic processing in terms of dynamic and non-modular mechanisms.     

Spousal agreement on preferred waiting time to next birth in sub-Saharan Africa

This study investigates how various social, demographic and economic factors affect spousal agreement on preferred waiting time to next birth. Data for matched cohabiting couples from ten Demographic and Health Surveys in sub-Saharan Africa (Benin, Burkina Faso, Ghana, Guinea, Mali, Ethiopia, Kenya, Mozambique, Zambia and Zimbabwe), conducted between 2003 and 2006, were analysed to compare reported waiting time to next birth by the husband and the wife. Couples where the reported waiting time to next birth was the same for both partners (difference is 0 months) were defined as having agreement on waiting time to next birth. In sub-Saharan Africa, spousal agreement on waiting time to next birth was found to be associated with wanting the next child sooner. When the spouses disagree on waiting time to next birth, the wives want to wait longer than their husbands in most cases. Additionally, the study found that demographic factors are the primary determinants of spousal agreement on waiting time to next birth, not socioeconomic factors. The strongest predictors of spousal agreement on waiting time to next birth were number of living children, difference between the number of ideal and living children and wife's age. Couples with fewer children, a younger wife and those with a difference of five or more children between ideal and living number of children were more likely to agree on waiting time to next birth. Effects of socioeconomic factors, such as education and wealth status, on spousal agreement on waiting time to next birth were generally weak and inconsistent. The findings highlight some of the challenges in developing programmes to promote spousal communication and birth spacing and underscore the need for programmes to be gender-sensitive.