A 15 year slow-slip event on the Sunda megathrust offshore Sumatra

In the Banyak Islands of Sumatra, coral microatoll records reveal a 15 year-long reversal of interseismic vertical displacement from subsidence to uplift between 1966 and 1981. To explain these coral observations, we test four hypotheses, including regional sea level changes and various tectonic mechanisms. Our results show that the coral observations likely reflect a 15 year-long slow-slip event (SSE) on the Sunda megathrust. This long-duration SSE exceeds the duration of previously reported SSEs and demonstrates the importance of multidecade geodetic records in illuminating the full spectrum of megathrust slip behavior at subduction zones

Neural basis of implicit motor sequence learning : Modulation of cortical power

Implicit sequence learning describes the acquisition of serially ordered movements and sequentially structured cognitive information, that occurs without awareness. Theta, alpha and beta cortical oscillations are present during implicit motor sequence learning, but their role in this process is unclear. The current study addressed this gap in the literature. A total of 50 healthy adults aged between 19 and 37 years participated in the study. Implicit motor sequence learning was examined using the Serial Reaction Time task where participants unknowingly repeat a sequence of finger movements in response to a visual stimulus. Sequence learning was examined by comparing reaction times and oscillatory power between sequence trials and a set of control trials comprising random stimulus presentations. Electroencephalography was recorded as participants completed the task. Analyses of the behavioral data revealed participants learnt the sequence. Analyses of oscillatory activity, using permutation testing, revealed sequence learning was associated with a decrease in theta band (4–7 Hz) power recorded over frontal and central electrode sites. Sequence learning effects were not observed in the alpha (7–12 Hz) or beta bands (12–20 Hz). Even though alpha and beta power modulations have long been associated with executing a motor response, it seems theta power is a correlate of sequence learning in the manual domain. Theta power modulations on the serial reaction time task may reflect disengagement of attentional resources, either promoting or occurring as a consequence of implicit motor sequence learnin

Modulation of control: Can HD-tDCS targeting the dACC reduce impulsivity?

Background: The dorsal anterior cingulate cortex (dACC) and its neurocircuits are central in impulsivity, and maladaptive dACC activity has been implicated in psychological disorders

Detectability of Plasmodium falciparum clones

BACKGROUND: In areas of high transmission people often harbour multiple clones of Plasmodium falciparum, but even PCR-based diagnostic methods can only detect a fraction (the detectability, q) of all clones present in a host. Accurate measurements of detectability are desirable since it affects estimates of multiplicity of infection, prevalence, and frequency of breakthrough infections in clinical drug trials. Detectability can be estimated by typing repeated samples from the same host but it has been unclear what should be the time interval between the samples and how the data should be analysed. METHODS: A longitudinal molecular study was conducted in the Kassena-Nankana district in northern Ghana. From each of the 80 participants, four finger prick samples were collected over a period of 8 days, and tested for presence of different Merozoite Surface Protein (msp) 2 genotypes. Implications for estimating q were derived from these data by comparing the fit of statistical models of serial dependence and over-dispersion. RESULTS: The distribution of the frequencies of detection for msp2 genotypes was close to binomial if the time span between consecutive blood samples was at least 7 days. For shorter intervals the probabilities of detection were positively correlated, i.e. the shorter the interval between two blood collections, the more likely the diagnostic results matched for a particular genotype. Estimates of q were rather insensitive to the statistical model fitted. CONCLUSIONS: A simple algorithm based on analysing blood samples collected 7 days apart is justified for generating robust estimates of detectability. The finding of positive correlation of detection probabilities for short time intervals argues against imperfect detection being directly linked to the 48-hour periodicity of P. falciparum. The results suggest that the detectability of a given parasite clone changes over time, at an unknown rate, but fast enough to regard blood samples taken one week apart as statistically independent

A passion for respect: On understanding the role of human needs and morality

In the present paper, we stress the importance of the concept respect in a wide variety of social settings and provide a working definition of this concept by emphasizing how respect relates to the act of communicating full recognition to other people on the dimensions of belongingness and morality. Subsequently, in two separate parts, we discuss why respect is so desired and valued. The first part looks at respect as a means to fulfil important human social concerns (“respect as a means to an end”). The second part looks at the potential moral underpinnings of respect and thus interprets “respect as an end in itself.” Finally, it is suggested that both reasons to value respect explain respect effects as a function of the working selfconcept that is salient (i.e., pragmatic versus idealistic self)

A passion for respect: On understanding the role of human needs and morality

In the present paper, we stress the importance of the concept respect in a wide variety of social settings and provide a working definition of this concept by emphasizing how respect relates to the act of communicating full recognition to other people on the dimensions of belongingness and morality. Subsequently, in two separate parts, we discuss why respect is so desired and valued. The first part looks at respect as a means to fulfil important human social concerns (“respect as a means to an end”). The second part looks at the potential moral underpinnings of respect and thus interprets “respect as an end in itself.” Finally, it is suggested that both reasons to value respect explain respect effects as a function of the working selfconcept that is salient (i.e., pragmatic versus idealistic self)

MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy

An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified MECP2 as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly amplified across 18% of cancers, and many cancer cell lines have amplified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRAS(G12C)-addicted cell line after KRAS down-regulation, and activated KRAS rescues the growth of an MECP2-addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action

Managing Relationship Decay Network, Gender, and Contextual Effects

Relationships are central to human life strategies and have crucial fitness consequences. Yet, at the same time, they incur significant maintenance costs that are rarely considered in either social psychological or evolutionary studies. Although many social psychological studies have explored their dynamics, these studies have typically focused on a small number of emotionally intense ties, whereas social networks in fact consist of a large number of ties that serve a variety of different functions. In this study, we examined how entire active personal networks changed over 18 months across a major life transition. Family relationships and friendships differed strikingly in this respect. The decline in friendship quality was mitigated by increased effort invested in the relationship, but with a striking gender difference: relationship decline was prevented most by increased contact frequency (talking together) for females but by doing more activities together in the case of males

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.