Impact of Chronic Sleep Disturbance for People Living With T1 Diabetes.

AIM: The aim was to explore personal experiences and to determine the impact of impaired sleep on well-being and diabetes-related activities/decision making among a cohort of people living with T1D. METHOD: Adults with T1D over the age of 18 and parents/carers of children with T1D were invited to complete an online questionnaire about their quality and quantity of sleep. Questions included impact of sleep on diabetes-related decision making, effective calculation of bolus doses, important aspects of psychosocial functioning, and frequency of waking. Diasend download data were used to objectively determine frequency of nocturnal blood glucose testing in children. RESULTS: A total of 258 parent/carer participants (n = 221 female, 85.6%) and 192 adults with T1D (n = 145, 75.5% female, age range 19 to 89 years) took part. In all, 239 parents/carers and 160 adults believed waking in the night has an impact on their usual daily functioning. Of these, 236 parents/carers and 151 (64%) adults reported the impact as negative. Chronic sleep interruption was associated with detrimental impact on mood, work, family relationships, ability to exercise regularly, ability to eat healthily, and happiness. CONCLUSION: Chronic sleep interruption is highly prevalent in adults with T1D and parents/carers of children with T1D with negative effects on daily functioning and well-being. Appropriate interventions are required to alleviate this burden of T1D, address modifiable risk factors for nocturnal hypoglycemia, and reduce the (perceived) need for nocturnal waking

Informal Caregivers' Experiences and Needs When Caring for a Relative With Heart Failure: An Interview Study

Background: Informal caregivers play an important role for persons with heart failure in strengthening medication adherence, encouraging self-care, and identifying deterioration in health status. Caring for a relative with heart failure can affect informal caregivers' well-being and cause caregiver burden. Objective: The objective of this study was to explore informal caregivers' experiences and needs when caring for a relative with heart failure living in their own home. Methods: The study has a qualitative design with an inductive approach. Interviews were conducted with 14 informal caregivers. Data were analyzed using qualitative content analysis. Results: Two themes emerged: "living in a changed existence" and "struggling and sharing with healthcare." The first theme describes informal caregivers' experiences, needs, and ways of moving forward when living in a changed existence with their relative. Informal caregivers were responsible for the functioning of everyday life, which challenged earlier established roles and lifestyle. They experienced an ever-present uncertainty related to the relative's impending sudden deterioration and to lack of knowledge about the condition. Incongruence was expressed between their own and their relative's understanding and acceptance of the heart failure condition. They also expressed being at peace with their relative and managed to restore new strength and motivation to care. The second theme describes informal caregivers' experiences, needs, and ways in which they handled the healthcare. They felt counted upon but not accounted for, as their care was taken for granted while their need to be seen and acknowledged by healthcare professionals was not met. Informal caregivers experienced an ever-present uncertainty regarding their lack of involvement with healthcare. The lack of involvement with healthcare had a negative impact on the relationship between informal caregivers and their relative due to the mutual loss of important information about changes in medication regimens and the relative's symptoms and well-being. Another cause of negative impact was the lack of opportunity to talk with healthcare professionals about the emotional and relational consequences of heart failure. Healthcare professionals had provided them neither with knowledge on heart failure nor with information on support groups in the municipality. Informal caregivers captured their own mandate through acting as deputies for their relative and claiming their rights of involvement in their relative's healthcare. They also felt confident despite difficult circumstances. The direct access to the medical clinic was a source of relief and they appreciated the contacts with the registered nurses specialized in heart failure. Informal caregivers' own initiatives to participate in meetings were positively received by healthcare professionals. Conclusions: Informal caregivers' daily life involves decisive changes that are experienced as burdensome. They handled their new situations using different strategies to preserve a sense of "self" and of "us." Informal caregivers express a need for more involvement with healthcare professionals, which may facilitate informal caregivers' situation and improve the dyadic congruence in the relation with their relative

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Constraining the magnitude of the Chiral Magnetic Effect with Event Shape Engineering in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76$ TeV

In ultrarelativistic heavy-ion collisions, the event-by-event variation of the elliptic flow $v_2$ reflects fluctuations in the shape of the initial state of the system. This allows to select events with the same centrality but different initial geometry. This selection technique, Event Shape Engineering, has been used in the analysis of charge-dependent two- and three-particle correlations in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}} =2.76$ TeV. The two-particle correlator $\langle \cos(\varphi_\alpha - \varphi_\beta) \rangle$, calculated for different combinations of charges $\alpha$ and $\beta$, is almost independent of $v_2$ (for a given centrality), while the three-particle correlator $\langle \cos(\varphi_\alpha + \varphi_\beta - 2\Psi_2) \rangle$ scales almost linearly both with the event $v_2$ and charged-particle pseudorapidity density. The charge dependence of the three-particle correlator is often interpreted as evidence for the Chiral Magnetic Effect (CME), a parity violating effect of the strong interaction. However, its measured dependence on $v_2$ points to a large non-CME contribution to the correlator. Comparing the results with Monte Carlo calculations including a magnetic field due to the spectators, the upper limit of the CME signal contribution to the three-particle correlator in the 10-50% centrality interval is found to be 26-33% at 95% confidence level.Comment: 20 pages, 6 captioned figures, 1 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/382

Measurement of the production of charm jets tagged with D0^{0} mesons in pp collisions at s\sqrt{s}= 7 TeV

The production of charm jets in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=7$ TeV was measured with the ALICE detector at the CERN Large Hadron Collider. The measurement is based on a data sample corresponding to a total integrated luminosity of $6.23$ ${\rm nb}^{-1}$, collected using a minimum-bias trigger. Charm jets are identified by the presence of a D$^0$ meson among their constituents. The D$^0$ mesons are reconstructed from their hadronic decay D$^0\rightarrow$K$^{-}\pi^{+}$. The D$^0$-meson tagged jets are reconstructed using tracks of charged particles (track-based jets) with the anti-$k_{\mathrm{T}}$ algorithm in the jet transverse momentum range $5<p_{\rm{T,jet}}^{\mathrm{ch}}<30$ ${\rm GeV/}c$ and pseudorapidity $|\eta_{\rm jet}|<0.5$. The fraction of charged jets containing a D$^0$-meson increases with $p_{\rm{T,jet}}^{\rm{ch}}$ from $0.042 \pm 0.004\, \mathrm{(stat)} \pm 0.006\, \mathrm{(syst)}$ to $0.080 \pm 0.009\, \rm{(stat)} \pm 0.008\, \rm{(syst)}$. The distribution of D$^0$-meson tagged jets as a function of the jet momentum fraction carried by the D$^0$ meson in the direction of the jet axis ($z_{||}^{\mathrm{ch}}$) is reported for two ranges of jet transverse momenta, $5<p_{\rm{T,jet}}^{\rm{ch}}<15$ ${\rm GeV/}c$ and $15<p_{\rm{T,jet}}^{\rm{ch}}<30$ ${\rm GeV/}c$ in the intervals $0.2<z_{||}^{\rm{ch}}<1.0$ and $0.4<z_{||}^{\rm{ch}}<1.0$, respectively. The data are compared with results from Monte Carlo event generators (PYTHIA 6, PYTHIA 8 and Herwig 7) and with a Next-to-Leading-Order perturbative Quantum Chromodynamics calculation, obtained with the POWHEG method and interfaced with PYTHIA 6 for the generation of the parton shower, fragmentation, hadronisation and underlying event.Comment: 29 pages, 8 captioned figures, 3 tables, authors from page 24, published version, figures at http://alice-publications.web.cern.ch/node/525

Measurement of Λ (1520) production in pp collisions at √s=7TeV and p–Pb collisions at √sNN=5.02TeV

The production of the Λ (1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s=7TeV and in p–Pb collisions at sNN=5.02TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Λ (1520) → pK - and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and p–Pb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (π, K, KS0, p, Λ) describes the shape of the Λ (1520) transverse momentum distribution up to 3.5GeV/c in p–Pb collisions. In the framework of this model, this observation suggests that the Λ (1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Λ (1520) to the yield of the ground state particle Λ remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in p–Pb collisions on the Λ (1520) yield

Measurement of prompt D0, D+, D*+, and DS+ production in p–Pb collisions at √sNN = 5.02 TeV

The measurement of the production of prompt D0, D+, D*+, and DS+ mesons in proton–lead (p–Pb) collisions at the centre-of-mass energy per nucleon pair of sNN = 5.02 TeV, with an integrated luminosity of 292 ± 11 μb−1, are reported. Differential production cross sections are measured at mid-rapidity (−0.96 &lt; ycms&lt; 0.04) as a function of transverse momentum (pT) in the intervals 0 &lt; pT&lt; 36 GeV/c for D0, 1 &lt; pT&lt; 36 GeV/c for D+ and D*+, and 2 &lt; pT&lt; 24 GeV/c for D+ mesons. For each species, the nuclear modification factor RpPb is calculated as a function of pT using a proton-proton (pp) ref- erence measured at the same collision energy. The results are compatible with unity in the whole pT range. The average of the non-strange D mesons RpPb is compared with theoretical model predictions that include initial-state effects and parton transport model predictions. The pT dependence of the D0, D+, and D*+ nuclear modification factors is also reported in the interval 1 &lt; pT&lt; 36 GeV/c as a function of the collision centrality, and the central-to-peripheral ratios are computed from the D-meson yields measured in different centrality classes. The results are further compared with charged-particle measurements and a similar trend is observed in all the centrality classes. The ratios of the pT-differential cross sections of D0, D+, D*+, and DS+ mesons are also reported. The DS+ and D+ yields are compared as a function of the charged-particle multiplicity for several pT intervals. No modification in the relative abundances of the four species is observed with respect to pp collisions within the statistical and systematic uncertainties. [Figure not available: see fulltext.]

Measurement of electrons from heavy-flavour hadron decays as a function of multiplicity in p-Pb collisions at √sNN = 5.02 TeV

The multiplicity dependence of electron production from heavy-flavour hadron decays as a function of transverse momentum was measured in p-Pb collisions at sNN = 5.02 TeV using the ALICE detector at the LHC. The measurement was performed in the centre-of-mass rapidity interval −1.07 &lt; ycms&lt; 0.14 and transverse momentum interval 2 &lt; pT&lt; 16 GeV/c. The multiplicity dependence of the production of electrons from heavy-flavour hadron decays was studied by comparing the pT spectra measured for different multiplicity classes with those measured in pp collisions (QpPb) and in peripheral p-Pb collisions (Qcp). The QpPb results obtained are consistent with unity within uncertainties in the measured pT interval and event classes. This indicates that heavy-flavour decay electron production is consistent with binary scaling and independent of the geometry of the collision system. Additionally, the results suggest that cold nuclear matter effects are negligible within uncertainties, in the production of heavy-flavour decay electrons at midrapidity in p-Pb collisions. [Figure not available: see fulltext.

An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ.

Passive immunization against β-amyloid (Aβ) has become an increasingly desirable strategy as a therapeutic treatment for Alzheimer's disease (AD). However, traditional passive immunization approaches carry the risk of Fcγ receptor-mediated overactivation of microglial cells, which may contribute to an inappropriate proinflammatory response leading to vasogenic edema and cerebral microhemorrhage. Here, we describe the generation of a humanized anti-Aβ monoclonal antibody of an IgG4 isotype, known as MABT5102A (MABT). An IgG4 subclass was selected to reduce the risk of Fcγ receptor-mediated overactivation of microglia. MABT bound with high affinity to multiple forms of Aβ, protected against Aβ1-42 oligomer-induced cytotoxicity, and increased uptake of neurotoxic Aβ oligomers by microglia. Furthermore, MABT-mediated amyloid plaque removal was demonstrated using in vivo live imaging in hAPP((V717I))/PS1 transgenic mice. When compared with a human IgG1 wild-type subclass, containing the same antigen-binding variable domains and with equal binding to Aβ, MABT showed reduced activation of stress-activated p38MAPK (p38 mitogen-activated protein kinase) in microglia and induced less release of the proinflammatory cytokine TNFα. We propose that a humanized IgG4 anti-Aβ antibody that takes advantage of a unique Aβ binding profile, while also possessing reduced effector function, may provide a safer therapeutic alternative for passive immunotherapy for AD. Data from a phase I clinical trial testing MABT is consistent with this hypothesis, showing no signs of vasogenic edema, even in ApoE4 carriers