Fitness benefits of prolonged post-reproductive lifespan in women

Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Familial Linkage between Neuropsychiatric Disorders and Intellectual Interests

From personality to neuropsychiatric disorders, individual differences in brain function are known to have a strong heritable component. Here we report that between close relatives, a variety of neuropsychiatric disorders covary strongly with intellectual interests. We surveyed an entire class of high-functioning young adults at an elite university for prospective major, familial incidence of neuropsychiatric disorders, and demographic and attitudinal questions. Students aspiring to technical majors (science/mathematics/engineering) were more likely than other students to report a sibling with an autism spectrum disorder (p = 0.037). Conversely, students interested in the humanities were more likely to report a family member with major depressive disorder (p = 8.8×10−4), bipolar disorder (p = 0.027), or substance abuse problems (p = 1.9×10−6). A combined PREdisposition for Subject MattEr (PRESUME) score based on these disorders was strongly predictive of subject matter interests (p = 9.6×10−8). Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests

Ion implantation in nanodiamonds: Size effect and energy dependence

Nanoparticles are ubiquitous in nature and are increasingly important for technology. They are subject to bombardment by ionizing radiation in a diverse range of environments. In particular, nanodiamonds represent a variety of nanoparticles of significant fundamental and applied interest. Here we present a combined experimental and computational study of the behaviour of nanodiamonds under irradiation by xenon ions. Unexpectedly, we observed a pronounced size effect on the radiation resistance of the nanodiamonds: particles larger than 8 nm behave similarly to macroscopic diamond (i.e. characterized by high radiation resistance) whereas smaller particles can be completely destroyed by a single impact from an ion in a defined energy range. This latter observation is explained by extreme heating of the nanodiamonds by the penetrating ion. The obtained results are not limited to nanodiamonds, making them of interest for several fields, putting constraints on processes for the controlled modification of nanodiamonds, on the survival of dust in astrophysical environments, and on the behaviour of actinides released from nuclear waste into the environment

Sensitivity of the human auditory cortex to acoustic degradation of speech and non-speech sounds

The perception of speech is usually an effortless and reliable process even in highly adverse listening conditions. In addition to external sound sources, the intelligibility of speech can be reduced by degradation of the structure of speech signal itself, for example by digital compression of sound. This kind of distortion may be even more detrimental to speech intelligibility than external distortion, given that the auditory system will not be able to utilize sound source-specific acoustic features, such as spatial location, to separate the distortion from the speech signal. The perceptual consequences of acoustic distortions on speech intelligibility have been extensively studied. However, the cortical mechanisms of speech perception in adverse listening conditions are not well known at present, particularly in situations where the speech signal itself is distorted. The aim of this thesis was to investigate the cortical mechanisms underlying speech perception in conditions where speech is less intelligible due to external distortion or as a result of digital compression. In the studies of this thesis, the intelligibility of speech was varied either by digital compression or addition of stochastic noise. Cortical activity related to the speech stimuli was measured using magnetoencephalography (MEG). The results indicated that degradation of speech sounds by digital compression enhanced the evoked responses originating from the auditory cortex, whereas addition of stochastic noise did not modulate the cortical responses. Furthermore, it was shown that if the distortion was presented continuously in the background, the transient activity of auditory cortex was delayed. On the perceptual level, digital compression reduced the comprehensibility of speech more than additive stochastic noise. In addition, it was also demonstrated that prior knowledge of speech content enhanced the intelligibility of distorted speech substantially, and this perceptual change was associated with an increase in cortical activity within several regions adjacent to auditory cortex. In conclusion, the results of this thesis show that the auditory cortex is very sensitive to the acoustic features of the distortion, while at later processing stages, several cortical areas reflect the intelligibility of speech. These findings suggest that the auditory system rapidly adapts to the variability of the auditory environment, and can efficiently utilize previous knowledge of speech content in deciphering acoustically degraded speech signals.Puheen havaitseminen on useimmiten vaivatonta ja luotettavaa myös erittäin huonoissa kuunteluolosuhteissa. Puheen ymmärrettävyys voi kuitenkin heikentyä ympäristön häiriölähteiden lisäksi myös silloin, kun puhesignaalin rakennetta muutetaan esimerkiksi pakkaamalla digitaalista ääntä. Tällainen häiriö voi heikentää ymmärrettävyyttä jopa ulkoisia häiriöitä voimakkaammin, koska kuulojärjestelmä ei pysty hyödyntämään äänilähteen ominaisuuksia, kuten äänen tulosuuntaa, häiriön erottelemisessa puheesta. Akustisten häiriöiden vaikutuksia puheen havaitsemiseen on tutkttu laajalti, mutta havaitsemiseen liittyvät aivomekanismit tunnetaan edelleen melko puutteelisesti etenkin tilanteissa, joissa itse puhesignaali on laadultaan heikentynyt. Tämän väitöskirjan tavoitteena oli tutkia puheen havaitsemisen aivomekanismeja tilanteissa, joissa puhesignaali on vaikeammin ymmärrettävissä joko ulkoisen äänilähteen tai digitaalisen pakkauksen vuoksi. Väitöskirjan neljässä osatutkimuksessa lyhyiden puheäänien ja jatkuvan puheen ymmärrettävyyttä muokattiin joko digitaalisen pakkauksen kautta tai lisäämällä puhesignaaliin satunnaiskohinaa. Puheärsykkeisiin liittyvää aivotoimintaa tutkittiin magnetoenkefalografia-mittauksilla. Tutkimuksissa havaittiin, että kuuloaivokuorella syntyneet herätevasteet voimistuivat, kun puheääntä pakattiin digitaalisesti. Sen sijaan puheääniin lisätty satunnaiskohina ei vaikuttanut herätevasteisiin. Edelleen, mikäli puheäänien taustalla esitettiin jatkuvaa häiriötä, kuuloaivokuoren aktivoituminen viivästyi häiriön intensiteetin kasvaessa. Kuuntelukokeissa havaittiin, että digitaalinen pakkaus heikentää puheäänien ymmärrettävyyttä voimakkaammin kuin satunnaiskohina. Lisäksi osoitettiin, että aiempi tieto puheen sisällöstä paransi merkittävästi häiriöisen puheen ymmärrettävyyttä, mikä heijastui aivotoimintaan kuuloaivokuoren viereisillä aivoalueilla siten, että ymmärrettävä puhe aiheutti suuremman aktivaation kuin heikosti ymmärrettävä puhe. Väitöskirjan tulokset osoittavat, että kuuloaivokuori on erittäin herkkä puheäänien akustisille häiriöille, ja myöhemmissä prosessoinnin vaiheissa useat kuuloaivokuoren viereiset aivoalueet heijastavat puheen ymmärrettävyyttä. Tulosten mukaan voi olettaa, että kuulojärjestelmä mukautuu nopeasti ääniympäristön vaihteluihin muun muassa hyödyntämällä aiempaa tietoa puheen sisällöstä tulkitessaan häiriöistä puhesignaalia

The Threshold Bias Model: A Mathematical Model for the Nomothetic Approach of Suicide

Comparative and predictive analyses of suicide data from different countries are difficult to perform due to varying approaches and the lack of comparative parameters.A simple model (the Threshold Bias Model) was tested for comparative and predictive analyses of suicide rates by age. The model comprises of a six parameter distribution that was applied to the USA suicide rates by age for the years 2001 and 2002. Posteriorly, linear extrapolations are performed of the parameter values previously obtained for these years in order to estimate the values corresponding to the year 2003. The calculated distributions agreed reasonably well with the aggregate data. The model was also used to determine the age above which suicide rates become statistically observable in USA, Brazil and Sri Lanka.The Threshold Bias Model has considerable potential applications in demographic studies of suicide. Moreover, since the model can be used to predict the evolution of suicide rates based on information extracted from past data, it will be of great interest to suicidologists and other researchers in the field of mental health

Development and Initial Validation of the PEG, a Three-item Scale Assessing Pain Intensity and Interference

Inadequate pain assessment is a barrier to appropriate pain management, but single-item “pain screening” provides limited information about chronic pain. Multidimensional pain measures such as the Brief Pain Inventory (BPI) are widely used in pain specialty and research settings, but are impractical for primary care. A brief and straightforward multidimensional pain measure could potentially improve initial assessment and follow-up of chronic pain in primary care. To develop an ultra-brief pain measure derived from the BPI. Development of a shortened three-item pain measure and initial assessment of its reliability, validity, and responsiveness. We used data from 1) a longitudinal study of 500 primary care patients with chronic pain and 2) a cross-sectional study of 646 veterans recruited from ambulatory care. Selected items assess average pain intensity (P), interference with enjoyment of life (E), and interference with general activity (G). Reliability of the three-item scale (PEG) was α = 0.73 and 0.89 in the two study samples. Overall, construct validity of the PEG was good for various pain-specific measures (r = 0.60–0.89 in Study 1 and r = 0.77–0.95 in Study 2), and comparable to that of the BPI. The PEG was sensitive to change and differentiated between patients with and without pain improvement at 6 months. We provide strong initial evidence for reliability, construct validity, and responsiveness of the PEG among primary care and other ambulatory clinic patients. The PEG may be a practical and useful tool to improve assessment and monitoring of chronic pain in primary care

Sustainable Financing of Innovative Therapies: A Review of Approaches

The process of innovation is inherently complex, and it occurs within an even more complex institutional environment characterized by incomplete information, market power, and externalities. There are therefore different competing approaches to supporting and financing innovation in medical technologies, which bring their own advantages and disadvantages. This article reviews value- and cost-based pricing, as well direct government funding, and cross-cutting institutional structures. It argues that performance-based risk-sharing agreements are likely to have little effect on the sustainability of financing; that there is a role for cost-based pricing models in some situations; and that the push towards longer exclusivity periods is likely contrary to the interests of industry

Geographical Representativeness of Published and Ongoing Randomized Controlled Trials. The Example of: Tobacco Consumption and HIV Infection

BACKGROUND: The challenge for evidence-based healthcare is to reduce mortality and the burden of diseases. This study aimed to compare where research is conducted to where research is needed for 2 public health priorities: tobacco consumption and HIV infection. METHODS: We identified randomized controlled trials (RCTs) included in Cochrane systematic reviews published between 1997 and 2007 and registered ongoing RCTs identified in January 2009 through the World Health Organization's International Clinical Trials Registry Platform (WHO-ICTRP) evaluating interventions aimed at reducing or stopping tobacco use and treating or preventing HIV infection. We used the WHO and World Bank reports to classify the countries by income level, as well as map the global burden of disease and mortality attributable to tobacco use and HIV infection to the countries where the trials performed. RESULTS: We evaluated 740 RCTs included in systematic reviews and 346 ongoing RCTs. For tobacco use, 4% of RCTs included in systematic reviews and 2% of ongoing trials were performed in low- and middle-income countries, even though these countries represented 70% of the mortality related to tobacco use. For HIV infection, 31% of RCTs included in systematic reviews and 33% of ongoing trials were performed in low- and middle-income countries, even though these countries represented 99% of the mortality related to HIV infection. CONCLUSIONS: Our results highlight an important underrepresentation of low- and middle-income countries in currently available evidence (RCTs included in systematic reviews) and awaiting evidence (registered ongoing RCTs) for reducing or stopping tobacco use and treating or preventing HIV infection

Integrated HIV Testing, Malaria, and Diarrhea Prevention Campaign in Kenya: Modeled Health Impact and Cost-Effectiveness

Efficiently delivered interventions to reduce HIV, malaria, and diarrhea are essential to accelerating global health efforts. A 2008 community integrated prevention campaign in Western Province, Kenya, reached 47,000 individuals over 7 days, providing HIV testing and counseling, water filters, insecticide-treated bed nets, condoms, and for HIV-infected individuals cotrimoxazole prophylaxis and referral for ongoing care. We modeled the potential cost-effectiveness of a scaled-up integrated prevention campaign.We estimated averted deaths and disability-adjusted life years (DALYs) based on published data on baseline mortality and morbidity and on the protective effect of interventions, including antiretroviral therapy. We incorporate a previously estimated scaled-up campaign cost. We used published costs of medical care to estimate savings from averted illness (for all three diseases) and the added costs of initiating treatment earlier in the course of HIV disease.Per 1000 participants, projected reductions in cases of diarrhea, malaria, and HIV infection avert an estimated 16.3 deaths, 359 DALYs and $85,113 in medical care costs. Earlier care for HIV-infected persons adds an estimated 82 DALYs averted (to a total of 442), at a cost of$37,097 (reducing total averted costs to $48,015). Accounting for the estimated campaign cost of$32,000, the campaign saves an estimated $16,015 per 1000 participants. In multivariate sensitivity analyses, 83$20.A mass, rapidly implemented campaign for HIV testing, safe water, and malaria control appears economically attractive