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\"Through case studies, this edited volume articulates why locally led peacebuilding matters, how it can prevent violence, and invites practitioners and scholars to critically examine the implications of locally led initiatives\"-- Provided by publisher.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

Autoantibodies targeting the intracellular 65-kDa isoform of glutamic acid decarboxylase (anti-GAD65) have been associated with a variety of autoimmune-related syndromes involving a spectrum of difficult-to-treat neurological disorders. However, the pathophysiological role of anti-GAD65 in neuroinflammation remains vague. Its understanding may be complicated by the possible pathogenic interaction between anti-GAD65 and potentially coexisting autoantibodies. We combined a broad spectrum of approaches ranging from antibody-antigen identification, immunoblotting, immunoprecipitation, mass-spectrometry, cell-based assays, subcellular binding pattern analysis in primary neuronal cultures, and immunohistochemistry to in vitro assays of neuronal uptake, viability, and multi-electrode arrays. In anti-GAD65-positive neurological patients, mass-spectrometric analysis revealed cytosolic 5'-nucleotidase 1 A (CN1A syn. NT5C1A) as the most abundant antigen. Subsequent screening of 118 anti-GAD65-positive patients revealed that 32 of them had additional autoantibodies targeting CN1A, which were also present in all available corresponding CSF samples. Limbic encephalitis was more often diagnosed in anti-CN1A/anti-GAD65-positive compared to the anti-GAD65-positive patients. Functionally, incubation of primary hippocampal neurons with anti-GAD65, but not with anti-CN1A, resulted in uptake into GABAergic neurons, neuronal cell death, and increased neuronal network activity. Moreover, simultaneous incubation with both antibodies (anti-CN1A/anti-GAD65) resulted in concomitant intraneuronal uptake in a concentration-dependent manner, which correlated with enhanced autophagy followed by massive neuronal death. GAD65 antibodies directly affect neuronal viability and network activity. Co-existing autoantibodies against CN1A, present in anti-GAD65-positive patients, enhance autophagy and subsequent neuronal death in vitro. Clinically, anti-GAD65-positive patients should be screened for anti-CN1A-associated diseases, and evaluation of anti-CN1A in anti-GAD65-related autoimmune conditions may clarify links between systemic autoimmunity and epilepsy.

We have proposed the possibility of a cost-efficient way to improve the detector performance for water Cherenkov detectors, by reflecting the usually lost light falling between photo-detectors onto the other side of the tank with retro-reflectors. Using a detector simulation based on optical measurements of retro-reflectors, we developed a convolutional neural network-based reconstruction algorithm. Here we report on the reconstruction performance for ring events in the energy scale expected for atmospheric and accelerator neutrinos under various candidate detector configurations.

After returning from Europe to the United States, on March 1, 2020, a symptomatic teacher received positive test results for severe acute respiratory syndrome coronavirus 2. Of the 21 students exposed to the teacher in the classroom, serologic results suggested past infection for 2. Classroom contact may result in virus transmission.

We characterized common exposures reported by a convenience sample of 202 US patients with coronavirus disease during January-April 2020 and identified factors associated with presumed household transmission. The most commonly reported settings of known exposure were households and healthcare facilities; among case-patients who had known contact with a confirmed case-patient compared with those who did not, healthcare occupations were more common. Among case-patients without known contact, use of public transportation was more common. Within the household, presumed transmission was highest from older (>65 years) index case-patients and from children to parents, independent of index case-patient age. These findings may inform guidance for limiting transmission and emphasize the value of testing to identify community-acquired infections.

Monkeypox, a zoonotic infection caused by an orthopoxvirus, is endemic in parts of Africa. On August 4, 2022, the U.S. Department of Health and Human Services declared the U.S. monkeypox outbreak, which began on May 17, to be a public health emergency (1,2). After detection of the first U.S. monkeypox case), CDC and health departments implemented enhanced monkeypox case detection and reporting. Among 2,891 cases reported in the United States through July 22 by 43 states, Puerto Rico, and the District of Columbia (DC), CDC received case report forms for 1,195 (41%) cases by July 27. Among these, 99% of cases were among men; among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before symptom onset. Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons. Forty-two percent of persons with monkeypox with available data did not report the typical prodrome as their first symptom, and 46% reported one or more genital lesions during their illness; 41% had HIV infection. Data suggest that widespread community transmission of monkeypox has disproportionately affected gay, bisexual, and other men who have sex with men and racial and ethnic minority groups. Compared with historical reports of monkeypox in areas with endemic disease, currently reported outbreak-associated cases are less likely to have a prodrome and more likely to have genital involvement. CDC and other federal, state, and local agencies have implemented response efforts to expand testing, treatment, and vaccination. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, while addressing equity, minimizing stigma, and maintaining vigilance for transmission in other populations. Clinicians should test patients with rash consistent with monkeypox, regardless of whether the rash is disseminated or was preceded by prodrome. Likewise, although most cases to date have occurred among gay, bisexual, and other men who have sex with men, any patient with rash consistent with monkeypox should be considered for testing. CDC is continually evaluating new evidence and tailoring response strategies as information on changing case demographics, clinical characteristics, transmission, and vaccine effectiveness become available. .

Background Autoantibodies targeting the intracellular 65-kDa isoform of glutamic acid decarboxylase (anti-GAD65) have been associated with a variety of autoimmune-related syndromes involving a spectrum of difficult-to-treat neurological disorders. However, the pathophysiological role of anti-GAD65 in neuroinflammation remains vague. Its understanding may be complicated by the possible pathogenic interaction between anti-GAD65 and potentially coexisting autoantibodies. Methods We combined a broad spectrum of approaches ranging from antibody-antigen identification, immunoblotting, immunoprecipitation, mass-spectrometry, cell-based assays, subcellular binding pattern analysis in primary neuronal cultures, and immunohistochemistry to in vitro assays of neuronal uptake, viability, and multi-electrode arrays. Results In anti-GAD65-positive neurological patients, mass-spectrometric analysis revealed cytosolic 5’-nucleotidase 1 A (CN1A syn. NT5C1A) as the most abundant antigen. Subsequent screening of 118 anti-GAD65-positive patients revealed that 32 of them had additional autoantibodies targeting CN1A, which were also present in all available corresponding CSF samples. Limbic encephalitis was more often diagnosed in anti-CN1A/anti-GAD65-positive compared to the anti-GAD65-positive patients. Functionally, incubation of primary hippocampal neurons with anti-GAD65, but not with anti-CN1A, resulted in uptake into GABAergic neurons, neuronal cell death, and increased neuronal network activity. Moreover, simultaneous incubation with both antibodies (anti-CN1A/anti-GAD65) resulted in concomitant intraneuronal uptake in a concentration-dependent manner, which correlated with enhanced autophagy followed by massive neuronal death. Conclusion GAD65 antibodies directly affect neuronal viability and network activity. Co-existing autoantibodies against CN1A, present in anti-GAD65-positive patients, enhance autophagy and subsequent neuronal death in vitro. Clinically, anti-GAD65-positive patients should be screened for anti-CN1A-associated diseases, and evaluation of anti-CN1A in anti-GAD65-related autoimmune conditions may clarify links between systemic autoimmunity and epilepsy. Significance What is already known on this topic – Even though autoantibodies against GAD65 protein have been identified in several autoimmune disorders their direct pathogenic effects are highly controversial and patients are often difficult to treat. What this study adds – Anti-GAD65-positive patients often have coexisting CN1A autoantibodies, leading to higher incidence of limbic encephalitis, increased neuronal activity, with combined autoantibody uptake enhancing neuronal death rate correlated with enhanced autophagy. How this study might affect research , practice or policy – Patients positive for anti-GAD65 should be screened for anti-CN1A-associated diseases, and broader evaluation of anti-CN1A in anti-GAD65-related autoimmune conditions (e.g., type 1 diabetes, vitiligo, Hashimoto’s thyroiditis) may clarify links between systemic autoimmunity and epilepsy. Bullet points Anti-GAD65-positive neurological patients show a high prevalence of coexisting autoantibodies against CN1A. CN1A/GAD65 autoantibody-positive patients are more often diagnosed with limbic encephalitis. Patient-derived GAD65 autoantibodies increase network activity in cultured neurons. Interneuronal dendritic uptake of anti-CN1A combined with anti-GAD65 leads to aggravated neurodegeneration associated with enhanced autophagy.

Abstract We have carried out $\\nu_{\\mu}$ charged-current interaction measurement on iron using an emulsion detector exposed to the T2K neutrino beam in the J-PARC neutrino facility. The data samples correspond to $4.0 \\times 10^{19}$ protons on target, and the neutrino mean energy is 1.49 GeV. The emulsion detector is suitable for precision measurements of charged particles produced in neutrino–iron interactions with a low momentum threshold thanks to a thin-layered structure and sub-$\\mu$m spatial resolution. The charged particles are successfully detected, and their multiplicities are measured using the emulsion detector. The cross section was measured to be $\\sigma^{\\mathrm{Fe}}_{\\mathrm{CC}} = (1.28 \\pm 0.11({\\mathrm{stat.}})^{+0.12}_{-0.11}({\\mathrm{syst.}})) \\times 10^{-38} \\, {\\mathrm{cm}}^{2}/{\\mathrm{nucleon}}$. The cross section in a limited kinematic phase space of induced muons, $\\theta_{\\mu} < 45^{\\circ}$ and $p_{\\mu} > 400 \\, {\\rm MeV}/c$, on iron was $\\sigma^{\\mathrm{Fe}}_{\\mathrm{CC \\hspace{1mm} phase \\hspace{0.5mm} space}} = (0.84 \\pm 0.07({\\mathrm{stat.}})^{+0.07}_{-0.06}({\\mathrm{syst.}})) \\times 10^{-38} \\, {\\mathrm{cm}}^{2}/{\\mathrm{nucleon}}$. The cross-section results are consistent with previous values obtained via different techniques using the same beamline, and they are reproduced well by current neutrino interaction models. These results demonstrate the capability of the detector in the detailed measurement of neutrino–nucleus interactions around the 1 GeV energy region.

The charge-conjugation and parity-reversal (CP) symmetry of fundamental particles is a symmetry between matter and antimatter. Violation of this CP symmetry was first observed in 1964 1 , and CP violation in the weak interactions of quarks was soon established 2 . Sakharov proposed 3 that CP violation is necessary to explain the observed imbalance of matter and antimatter abundance in the Universe. However, CP violation in quarks is too small to support this explanation. So far, CP violation has not been observed in non-quark elementary particle systems. It has been shown that CP violation in leptons could generate the matter–antimatter disparity through a process called leptogenesis 4 . Leptonic mixing, which appears in the standard model’s charged current interactions 5 , 6 , provides a potential source of CP violation through a complex phase δ CP , which is required by some theoretical models of leptogenesis 7 – 9 . This CP violation can be measured in muon neutrino to electron neutrino oscillations and the corresponding antineutrino oscillations, which are experimentally accessible using accelerator-produced beams as established by the Tokai-to-Kamioka (T2K) and NOvA experiments 10 , 11 . Until now, the value of δ CP has not been substantially constrained by neutrino oscillation experiments. Here we report a measurement using long-baseline neutrino and antineutrino oscillations observed by the T2K experiment that shows a large increase in the neutrino oscillation probability, excluding values of δ CP that result in a large increase in the observed antineutrino oscillation probability at three standard deviations (3 σ ). The 3 σ confidence interval for δ CP , which is cyclic and repeats every 2π, is [−3.41, −0.03] for the so-called normal mass ordering and [−2.54, −0.32] for the inverted mass ordering. Our results indicate CP violation in leptons and our method enables sensitive searches for matter–antimatter asymmetry in neutrino oscillations using accelerator-produced neutrino beams. Future measurements with larger datasets will test whether leptonic CP violation is larger than the CP violation in quarks. The T2K experiment constrains CP symmetry in neutrino oscillations, excluding 46% of possible values of the CP violating parameter at a significance of three standard deviations; this is an important milestone to test CP symmetry conservation in leptons and whether the Universe’s matter–antimatter imbalance originates from leptons.