Early signs of disease in type 1 diabetes

As a severe chronic disease with long-term complications, type 1 diabetes (T1D) is a burden to the patients and their families as well as a challenge to the health care system. T1D is a heterogeneous disease with a variety of etiologies and a wide range in the rate of progression to the disease. In order to prevent and treat T1D it would be important to identify measures that could be used to predict and monitor disease progression, as well as to further understand the molecular mechanisms involved. During the past 20 yr since its initiation, the Finnish Diabetes Prediction and Prevention Project (DIPP) has collected longitudinal biological samples from children with a human leukocyte antigen gene-conferred risk of T1D. This large sample collection has provided detailed sample series that enable studies to map the progression from health to disease, as well as the healthy maturation of risk-matched children. The DIPP samples have been used in a large body of research to elucidate the factors involved in the development of T1D. Interestingly, results from recent studies exploiting omics platforms have revealed that signs of the disease process can be detected very early on, even prior to appearance of the first T1D-associated antibodies, which are currently considered the earliest indications of the emerging disease. Identification and validation of multi-modal molecular markers will we hope provide a means to subgroup the heterogeneous group of T1D patients and enable prediction, diagnosis, and monitoring of T1D. Discovery of such markers is important in the design and testing of prevention and therapies for T1D</p

Efficient Production of Large 39K Bose-Einstein Condensates

We describe an experimental setup and the cooling procedure for producing 39K Bose-Einstein condensates of over 4x10^5 atoms. Condensation is achieved via a combination of sympathetic cooling with 87Rb in a quadrupole-Ioffe-configuration (QUIC) magnetic trap, and direct evaporation in a large volume crossed optical dipole trap, where we exploit the broad Feshbach resonance at 402 G to tune the 39K interactions from weak and attractive to strong and repulsive. In the same apparatus we create quasi-pure 87Rb condensates of over 8x10^5 atoms.Comment: 7 pages, 5 figures; figure font compatibility improve

Imaging Radiation Pneumonitis in a Rat Model of a Radiological Terrorism Incident

We have developed a rat model of single, sub-lethal thoracic irradiation. Our irradiation protocol is considered representative of exposures near the detonation site of a dirty bomb or small nuclear device. The model is being used to investigate techniques for identifying, triaging and treating possible victims. In addition to physiological markers of right ventricular hypertrophy, pulmonary vascular resistance, and arterial distensibility, we present two methods for quantifying microvascular density. We used methods including microfocal X-ray imaging to investigate changes in lung structure/function resulting from radiation exposure. Radiation pneumonitis is a complication in subjects receiving thoracic irradiation. A radiographic hallmark of acute radiation pneumonitis is a diffuse infiltrate corresponding to the radiation treatment field. We describe two methods for quantifying small artery dropout that occurs in the model at the same time-period. Rats were examined 3-days, 2-weeks, 1-month (m), 2-m, 5-m, and 12-m post-irradiation and compared with aged-matched controls. Right ventricular hypertrophy and increases in pulmonary vascular resistance were present during the pneumonitis phase. Vascular injury was dependent on dose and post-irradiation duration. Rats irradiated with 5 Gy had few detectable changes, whereas 10 Gy resulted in a significant decrease in both microvascular density and arterial distensibility around 2- m, the decrease in each lessening, but extending through 12-m. In conclusion, rats irradiated with a 10 Gy dose had changes in vascular structure concurrent with the onset of radiation pneumonitis that were detectable with our imaging techniques and these structural changes persist after resolution of the pneumonitis

Mitigation of Radiation Induced Pulmonary Vascular Injury by Delayed Treatment with Captopril

Background and Objective: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2 months post-exposure. In this study, we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods: Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2 months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2 weeks after radiation exposure, with two doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary haemodynamics, lung ACE activity, pulmonary arterial distensibility and peripheral vessel density. Results: Captopril, given at a vasoactive, but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly, these beneficial effects were observed even if drug therapy was delayed for up to 2 weeks after exposure. Conclusions: Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident

Can a Bose gas be saturated?

Bose-Einstein condensation is unique among phase transitions between different states of matter in the sense that it occurs even in the absence of interactions between particles. In Einstein's textbook picture of an ideal gas, purely statistical arguments set an upper bound on the number of particles occupying the excited states of the system, and condensation is driven by this saturation of the quantum vapour. Dilute ultracold atomic gases are celebrated as a realisation of Bose-Einstein condensation in close to its purely statistical form. Here we scrutinise this point of view using an ultracold gas of potassium (39K) atoms, in which the strength of interactions can be tuned via a Feshbach scattering resonance. We first show that under typical experi-mental conditions a partially condensed atomic gas strongly deviates from the textbook concept of a saturated vapour. We then use measurements at a range of interaction strengths and temperatures to extrapolate to the non-interacting limit, and prove that in this limit the behaviour of a Bose gas is consistent with the saturation picture. Finally, we provide evidence for the universality of our observations through additional measurements with a different atomic species, 87Rb. Our results suggest a new way of characterising condensation phenomena in different physical systems.Comment: 6 pages, 5 figure

The Mediating Role of Affective States in Short-Term Effects of Activity Engagement on Working Memory in Older Age

Introduction: It has been shown that activity engagement is associated with cognitive ability in older age, but mechanisms behind the associations have rarely been examined. Following a recent study which showed short-term effects of activity engagement on working memory performance appearing 6 h later, this study examined the mediating role of affective states in this process. Methods: For 7 times per day over 2 weeks, 150 Swiss older adults (aged 65–91 years) reported their present (sociocognitive/passive leisure) activities and affective states (high-arousal positive, low-arousal positive, high-arousal negative, and low-arousal negative) and completed an ambulatory working memory task on a smartphone. Results: Multilevel vector autoregression models showed that passive leisure activities were associated with worse working memory performance 6 h later. Passive leisure activities were negatively associated with concurrent high-arousal positive affect (and high-arousal negative affect); high-arousal positive affect was negatively associated with working memory performance 6 h later. A Sobel test showed a significant mediation effect of high-arousal positive affect linking the time-lagged relationship between passive leisure activities and working memory. Additionally, sociocognitive activities were associated with better working memory performance 6 h later. Sociocognitive activities were associated with concurrent higher high- and low-arousal positive affect, which, however, were not associated with working memory performance 6 h later. Thus, a mediation related to sociocognitive activities was not found. Discussion: Passive leisure activities could influence working memory performance through high-arousal positive affect within a timeframe of several hours. Results are discussed in relation to an emotional, and possibly a neuroendocrine, pathway explaining the time-lagged effects of affective states on working memory performance

Vascular Injury After Whole Thoracic X-Ray Irradiation in the Rat

Purpose To study vascular injury after whole thoracic irradiation with single sublethal doses of X-rays in the rat and to develop markers that might predict the severity of injury. Methods and Materials Rats that received 5- or 10-Gy thorax-only irradiation and age-matched controls were studied at 3 days, 2 weeks, and 1, 2, 5, and 12 months. Several pulmonary vascular parameters were evaluated, including hemodynamics, vessel density, total lung angiotensin-converting enzyme activity, and right ventricular hypertrophy. Results By 1 month, the rats in the 10-Gy group had pulmonary vascular dropout, right ventricular hypertrophy, increased pulmonary vascular resistance, increased dry lung weights, and decreases in total lung angiotensin-converting enzyme activity, as well as pulmonary artery distensibility. In contrast, irradiation with 5 Gy resulted in only a modest increase in right ventricular weight and a reduction in lung angiotensin-converting enzyme activity. Conclusion In a previous investigation using the same model, we observed that recovery from radiation-induced attenuation of pulmonary vascular reactivity occurred. In the present study, we report that deterioration results in several vascular parameters for ≤1 year after 10 Gy, suggesting sustained remodeling of the pulmonary vasculature. Our data support clinically relevant injuries that appear in a time- and dose-related manner after exposure to relatively low radiation doses

Nonverbal Synchrony Between Dyads as a Function of Protective Versus Acquisitive Self-Monitoring

Synchrony is coordinated nonverbal behavior between two individuals (Ramseyer & Tschacher, 2006). Dispositional differences in self-monitoring involves responsivity to others (Fuglestad & Snyder, 2010). Acquisitive self-monitoring entails responsivity for gain social/nonsocial rewards, whereas protective self-monitoring entails responsivity for avoiding social/nonsocial losses (Wilmot, 2015). We explored the connection between self-monitoring and nonverbal synchrony. Pairs of participants had 5-minute conversation on a non-controversial topic to control for the influence of affect on synchrony (Tschacher et al., 2014). We utilized Motion Energy Analysis and Windowed Crossed Correlation software to quantify nonverbal synchrony. Participants completed the 25-item Self-Monitoring Scale (Snyder, 1974), and responses were score or protective and acquisitive impression management motives (Wilmot et al, 2017). Dyad self-monitoring was calculated as the product of partners’ self-monitoring scores. Controlling for self-reported partner familiarity, separate regression analyses revealed that protective, β=+.21, p = .048, but not acquisitive, β=+.11, p = .287, self-monitoring reliably predicted nonverbal synchrony. These findings extend the literature on (a) synchrony by identifying individual differences in this process and (b) self-monitoring by illuminating the two-dimensional nature of this individual difference variable. Future research should further extend these literatures by examining moderator (e.g., relationship closeness) and mediating (e.g., state anxiety) variables