Triplets, birthweight, and handedness

The mechanisms behind handedness formation in humans are still poorly understood. Very low birthweight is associated with higher odds of left-handedness, but whether this is due to low birthweight itself or premature birth is unknown. Handedness has also been linked to development, but the role of birthweight behind this association is unclear. Knowing that birthweight is lower in multiple births, triplets being about 1.5 kg lighter in comparison with singletons, and that multiples have a higher prevalence of left-handedness than singletons, we studied the association between birthweight and handedness in two large samples consisting exclusively of triplets from Japan (n = 1,305) and the Netherlands (n = 947). In both samples, left-handers had significantly lower birthweight (Japanese mean = 1,599 g [95% confidence interval (CI): 1,526–1,672 g]; Dutch mean = 1,794 g [95% CI: 1,709–1,879 g]) compared with right-handers (Japanese mean = 1,727 g [95% CI: 1,699–1,755 g]; Dutch mean = 1,903 g [95% CI: 1,867–1,938 g]). Within-family and between-family analyses both suggested that left-handedness is associated with lower birthweight, also when fully controlling for gestational age. Left-handers also had significantly delayed motor development and smaller infant head circumference compared with right-handers, but these associations diluted and became nonsignificant when controlling for birthweight. Our study in triplets provides evidence for the link between low birthweight and left-handedness. Our results also suggest that developmental differences between left- and right-handers are due to a shared etiology associated with low birthweight

Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors:The phase I/II first-in-human MATINS trial

Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab shows no dose-limiting toxicities in part I (n = 30) and no additional safety signals in part II (n = 108). Disease control (DC) rates of 25%–40% are observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor-positive breast, and biliary tract cancers. DC associates with improved survival in a landmark analysis and correlates with high pre-treatment intratumoral Clever-1 positivity and increasing on-treatment serum interferon γ (IFNγ) levels. Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and T cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer

Measuring MEG closer to the brain

Optically-pumped magnetometers (OPMs) have recently reached sensitivity levels required for magnetoencephalography (MEG). OPMs do not need cryogenics and can thus be placed within millimetres from the scalp into an array that adapts to the individual head size and shape, thereby reducing the distance from cortical sources to the sensors. Here, we quantified the improvement in recording MEG with hypothetical on-scalp OPM arrays compared to a 306-channel state-of-the-art SQUID array (102 magnetometers and 204 planar gradiometers). We simulated OPM arrays that measured either normal (nOPM; 102 sensors), tangential (tOPM; 204 sensors), or all components (aOPM; 306 sensors) of the magnetic field. We built forward models based on magnetic resonance images of 10 adult heads; we employed a three-compartment boundary element model and distributed current dipoles evenly across the cortical mantle. Compared to the SQUID magnetometers, nOPM and tOPM yielded 7.5 and 5.3 times higher signal power, while the correlations between the field patterns of source dipoles were reduced by factors of 2.8 and 3.6, respectively. Values of the field-pattern correlations were similar across nOPM, tOPM and SQUID gradiometers. Volume currents reduced the signals of primary currents on average by 10%, 72% and 15% in nOPM, tOPM and SQUID magnetometers, respectively. The information capacities of the OPM arrays were clearly higher than that of the SQUID array. The dipole-localization accuracies of the arrays were similar while the minimum-norm-based point-spread functions were on average 2.4 and 2.5 times more spread for the SQUID array compared to nOPM and tOPM arrays, respectively.Peer reviewe

Requirements for Coregistration Accuracy in On-Scalp MEG

| openaire: EC/H2020/678578/EU//HRMEGRecent advances in magnetic sensing has made on-scalp magnetoencephalography (MEG) possible. In particular, optically-pumped magnetometers (OPMs) have reached sensitivity levels that enable their use in MEG. In contrast to the SQUID sensors used in current MEG systems, OPMs do not require cryogenic cooling and can thus be placed within millimetres from the head, enabling the construction of sensor arrays that conform to the shape of an individual’s head. To properly estimate the location of neural sources within the brain, one must accurately know the position and orientation of sensors in relation to the head. With the adaptable on-scalp MEG sensor arrays, this coregistration becomes more challenging than in current SQUID-based MEG systems that use rigid sensor arrays. Here, we used simulations to quantify how accurately one needs to know the position and orientation of sensors in an on-scalp MEG system. The effects that different types of localisation errors have on forward modelling and source estimates obtained by minimum-norm estimation, dipole fitting, and beamforming are detailed. We found that sensor position errors generally have a larger effect than orientation errors and that these errors affect the localisation accuracy of superficial sources the most. To obtain similar or higher accuracy than with current SQUID-based MEG systems, RMS sensor position and orientation errors should be (Formula presented.) and (Formula presented.), respectively.Peer reviewe

Life course of Finnish persons with intellectual disabilities born 1898-1960 : a 35-year follow-up study

There are scanty data on the life course of people with intellectual disability (ID) based on a long-term follow up of an adequately big number of patients. In Finland, a nationwide representative sample of persons born in 1898-1960, so called Finland-in-Miniature sample, with suspected or known ID was studied in 1962 by physicians, psychologists and social scientists in order to determine the prevalence of ID and the corresponding need for care, training, health and social welfare services (Amnell 1966, Ruoppila 1966, Tarvainen 1966). At baseline, altogether 3 748 persons were examined, resulting 2 372 people being diagnosed as intellectually disabled. Two different subsamples of the baseline study were followed up 9 years later. These included two cohorts of people born in 1932 to 1946 and 1950 to 1954 and aged 7 to 13 (first school years) and 16 to 30 years (beginning the possible work career) at the baseline assessment. The aims of the new follow up study in 1998 were to examine the predictive validity of the original ID diagnoses, the life course of people with ID and studied but not diagnosed as ID in 1962, especially the use of different general services including hospital care, institutional care, out-patient care and housing services. Furthermore, our aim was to find out the age-related changes in physical, psychological and social functioning or general health condition of highly aged persons with ID. Ethically it is important to emphasise that the persons with ID, if possible, themselves answered in the interviews thus reflecting their own feelings. The drop out in different phases of the study has been very small. Thus the present study has many special strengths. We could use a nationwide representative large sample making possible analyses of age/cohort and gender difference as well as differences in the degree of ID. In this volume we have covered very broadly the life course of people with ID including their physical, psychological and social functioning or other words their health condition as a whole. The present volume ”Life Course and Intellectual Disability” includes 35 years´ follow up of a nationwide representative sample of originally 2372 subjects with ID. There are two main reasons which indicate the publication of these data. Firstly, the methodology part is complicated and originally reported in Finnish (Ruoppila 1966) and when forthcoming publications need to quote the methodology, it is easier for the readers to find out the essential reference. Secondly, the parts of this volume including methodology, predictive validity of diagnoses and use of services as a whole make a unity giving central information of the life course of people with ID. We believe that the present volume has worldwide implications and illustrates the relevant updated points on the life course of people with ID and thus helps the rational development of services for these people