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">5: thesis describes the social organisation of shepherding in a hill community, of 3500 inhabitants in central Sardinia. Its focus is on the consequences of the two major changes in the pastoral economy of the late 19th century: the conversion of public land into private property and the establishment of the dairy-processing industry in Sardinia. The landowners of the village were enabled to reinforce their dominant position and to draw shepherds into a network of patronage ties based on the access to land and the marketing of livestock produce. Among shepherds themselves new relations of solidarity and conflict were created in the countryside. The community became more rigidly stratified. These consequences are contrasted with the effects of the same changes among the villages of the central highlands of Sardinia where transhumant shepherds became more geographically and socially mobile. Relations set up in the course of this century between the shepherds of different communities are illustrated in the practice of livestock-rustling which constitutes at the same time a mode of prosecution of conflict in one community and an opportunity for capital accumulation by outsiders

We theoretically investigate and optimize the performance of four-wave mixing (FWM) in microring resonators (MRRs) integrated with two-dimensional (2D) layered graphene oxide (GO) films. Owing to the interaction between the MRRs and the highly nonlinear GO films as well as to the resonant enhancement effect, the FWM efficiency in GO-coated MRRs can be significantly improved. Based on previous experiments, we perform detailed analysis for the influence of the GO film parameters and MRR coupling strength on the FWM conversion efficiency (CE) of the hybrid MRRs. By optimizing the device parameters to balance the trade-off between the Kerr nonlinearity and loss, we achieve a high CE enhancement of ~ 18.6 dB relative to the uncoated MRR, which is ~ 8.3 dB higher than previous experimental results. The influence of photo-thermal changes in the GO films as well as variations in the MRR parameters such as the ring radius and waveguide dispersion on the FWM performance is also discussed. These results highlight the significantly improved FWM performance that can be achieved in MRRs incorporating GO films and provide a guide for optimizing their FWM performance.

We present theoretical designs of high performance optical filters in integrated silicon photonic nanowire resonators. We use mode interference in formed by zig-zag waveguide coupled Sagnac loop reflectors (ZWC-SLRs), tailored to achieve diverse filtering functions with good performance. These include compact bandpass filters with improved roll-off, optical analogues of Fano resonances with ultrahigh spectral extinction ratios (ERs) and slope rates, and resonance mode splitting with high ERs and low free spectral ranges. The analysis verifies the feasibility of multi-functional integrated photonic filters based on ZWC-SLR resonators for flexible spectral engineering in diverse applications.

Research on the efficacy of hypnosis applications continues to grow, but there remain major gaps between the science and clinical practice. One challenge has been a lack of consensus on what applications of hypnosis are efficacious based on research evidence. In 2018, six major hypnosis organizations collaborated to form a Task Force for Establishing Efficacy Standards for Clinical Hypnosis. This paper describes a Guideline for the Assessment of Efficacy of Clinical Hypnosis Applications developed by the Task Force which makes ten specific recommendations. The guideline is intended to be a tool for those who want to assess the quality of existing evidence on the efficacy of clinical hypnosis for any particular indication. The paper also discusses methodological issues in the interpretation and implementation of these guidelines. Future papers will report on the other products of the Hypnosis Efficacy Task Force, such as best practice recommendations for outcomes research in hypnosis, and an international survey of researchers and clinicians on current practice and attitudes about hypnosis.

Immigrants increasingly engage in homeland-oriented transnational institutional and non-institutional collective political action. Immigrant transnational political action, in turn, is largely conceptualised as being determined by either contexts of reception in receiving societies or diaspora policies emanating from immigrant origin countries. Thus, existing literature largely views immigrants’ transnational political action as a product of one particular political context or policy, which neglects to account for the ways in which their transnational politics are simultaneously embedded in and shaped by multiple political contexts. In this paper, we develop a nuanced account of the distinctive ways in which multiple political contexts shape the cross-border electoral, organisational and non-institutional collective action of immigrants and diaspora communities. By doing so, we transcend analytical emphases on receiving-society effects which largely view homeland-oriented politics through the lens of immigrant incorporation. We propose a triadic political opportunity approach to conceptualise how varied receiving-country, origin-country, and transnational political contexts shape immigrant transnational political action. We illustrate the utility of this approach by drawing on original research and secondary sources to demonstrate how receiving, origin and transnational political opportunity structures can facilitate and/or constrain immigrant transnational political action. We conclude with a discussion of potential applications of our approach for future research.

We report optical neuromorphic processors based on Kerr micro-combs that are programmable, scalable and ultra-high speed. We demonstrate a perceptron at 11.9Giga-OPS at 8 bits, or 95.2 Gbps, and a convolutional accelerator at 11TeraOPs/s.

Optical artificial neural networks (ONNs) have significant potential for ultra-high computing speed and energy efficiency. We report a new approach to ONNs based on integrated Kerr micro-combs that is programmable, highly scalable and capable of reaching ultra-high speeds, demonstrating the building block of the ONN — a single neuron perceptron — by mapping synapses onto 49 wavelengths to achieve a single-unit throughput of 11.9 Giga-OPS at 8 bits per OP, or 95.2 Gbps. We test the perceptron on handwritten-digit recognition and cancer-cell detection — achieving over 90% and 85% accuracy, respectively. By scaling the perceptron to a deep learning network using off-the-shelf telecom technology we can achieve high throughput operation for matrix multiplication for real-time massive data processing.

We experimentally demonstrate enhanced four-wave mixing in micro-ring resonators (MRRs) integrated with graphene oxide films. We achieve up to ~7.6-dB enhancement in conversion efficiency for a uniformly coated MRR and ~10.3-dB for a patterned device.

Importance In Huntington disease (HD), mutation severity is defined by the length of the CAG trinucleotide sequence, a well-known predictor of clinical onset age. The association with disease trajectory is less well characterized. Quantifiable summary measures of trajectory applicable over decades of early disease progression are lacking. An accurate model of the age-CAG association with early progression is critical to clinical trial design, informing both sample size and intervention timing. Objective To succinctly capture the decades-long early progression of HD and its dependence on CAG repeat length. Design, Setting, and Participants Prospective study at 4 academic HD treatment and research centers. Participants were the combined sample from the TRACK-HD and Track-On HD studies consisting of 290 gene carriers (presymptomatic to stage II), recruited from research registries at participating centers, and 153 nonbiologically related controls, generally spouses or friends. Recruitment was targeted to match a balanced, prespecified spectrum of age, CAG repeat length, and diagnostic status. In the TRACK-HD and Track-On HD studies, 13 and 5 potential participants, respectively, failed study screening. Follow-up ranged from 0 to 6 years. The study dates were January 2008 to November 2014. These analyses were performed between December 2015 and January 2019. Main Outcomes and Measures The outcome measures were principal component summary scores of motor-cognitive function and of brain volumes. The main outcome was the association of these scores with age and CAG repeat length. Results We analyzed 2065 visits from 443 participants (247 female [55.8%]; mean [SD] age, 44.4 [10.3] years). Motor-cognitive measures were highly correlated and had similar CAG repeat length–dependent associations with age. A composite summary score accounted for 67.6% of their combined variance. This score was well approximated by a score combining 3 items (total motor score, Symbol Digit Modalities Test, and Stroop word reading) from the Unified Huntington’s Disease Rating Scale. For either score, initial progression age and then acceleration rate were highly CAG repeat length dependent. The acceleration continues through at least stage II disease. In contrast, 3 distinct patterns emerged among brain measures (basal ganglia, gray matter, and a combination of whole-brain, ventricular, and white matter volumes). The basal ganglia pattern showed considerable change in even the youngest participants but demonstrated minimal acceleration of loss with aging. Each clinical and brain summary score was strongly associated with the onset and rate of decline in total functional capacity. Conclusions and Relevance Results of this study suggest that succinct summary measures of function and brain loss characterize HD progression across a wide disease span. CAG repeat length strongly predicts their decline rate. This work aids our understanding of the age and CAG repeat length–dependent association between changes in the brain and clinical manifestations of HD.

The mismatch repair gene MSH3 has been implicated as a genetic modifier of the CAG·CTG repeat expansion disorders Huntington's disease and myotonic dystrophy type 1. A recent Huntington's disease genome-wide association study found rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated with progression in Huntington's disease. Using Illumina sequencing in Huntington's disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG·CTG expansion (P = 0.004) and delayed disease onset (P = 0.003) in both Huntington's disease and myotonic dystrophy type 1, and slower progression (P = 3.86 × 10-7) in Huntington's disease. RNA-Seq of whole blood in the Huntington's disease subjects found that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the Huntington's disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington's disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion diseases.

Background Cognitive and motor task performance in premanifest Huntington's disease (HD) gene-carriers is often within normal ranges prior to clinical diagnosis, despite loss of brain volume in regions involved in these tasks. This indicates ongoing compensation, with the brain maintaining function in the presence of neuronal loss. However, thus far, compensatory processes in HD have not been modeled explicitly. Using a new model, which incorporates individual variability related to structural change and behavior, we sought to identify functional correlates of compensation in premanifest-HD gene-carriers. Methods We investigated the modulatory effects of regional brain atrophy, indexed by structural measures of disease load, on the relationship between performance and brain activity (or connectivity) using task-based and resting-state functional MRI. Findings Consistent with compensation, as atrophy increased performance-related activity increased in the right parietal cortex during a working memory task. Similarly, increased functional coupling between the right dorsolateral prefrontal cortex and a left hemisphere network in the resting-state predicted better cognitive performance as atrophy increased. Such patterns were not detectable for the left hemisphere or for motor tasks. Interpretation Our findings provide evidence for active compensatory processes in premanifest-HD for cognitive demands and suggest a higher vulnerability of the left hemisphere to the effects of regional atrophy., Highlights • Huntington's disease (HD) is an ideal model for studying the earliest stages of neurodegeneration. • Pre-clinical HD gene-carriers maintain normal behavior across motor and cognitive domains despite neuronal degeneration. • We characterized neural compensation using functional MRI in combination with measures of disease load and task performance. • Evidence of hemisphere-specific compensation provides potential targets for future therapeutic trials in neurodegeneration. We have developed a model which characterizes compensation in preclinical HD using functional MRI, volumetric disease load and task performance. By explicitly testing the relationship between cognitive performance and brain activity or connectivity, we have demonstrated that those closest to clinical diagnosis experience functional deterioration within the left hemisphere of the brain and localized compensation in the right. This pattern provides potential targets for future testing of HD modifying agents. Furthermore, HD acts as a model for studying the earliest stages of neurodegeneration and this new model of compensation can potentially be extended to other neurodegenerative diseases.

Background The earliest white matter changes in Huntington’s disease are seen before disease onset in the premanifest stage around the striatum, within the corpus callosum, and in posterior white matter tracts. While experimental evidence suggests that these changes may be related to abnormal gene transcription, we lack an understanding of the biological processes driving this regional vulnerability. Methods Here, we investigate the relationship between regional transcription in the healthy brain, using the Allen Institute for Brain Science transcriptome atlas, and regional white matter connectivity loss at three time points over 24 months in subjects with premanifest Huntington’s disease relative to control participants. The baseline cohort included 72 premanifest Huntington’s disease participants and 85 healthy control participants. Results We show that loss of corticostriatal, interhemispheric, and intrahemispheric white matter connections at baseline and over 24 months in premanifest Huntington’s disease is associated with gene expression profiles enriched for synaptic genes and metabolic genes. Corticostriatal gene expression profiles are predominately associated with motor, parietal, and occipital regions, while interhemispheric expression profiles are associated with frontotemporal regions. We also show that genes with known abnormal transcription in human Huntington’s disease and animal models are overrepresented in synaptic gene expression profiles, but not in metabolic gene expression profiles. Conclusions These findings suggest a dual mechanism of white matter vulnerability in Huntington’s disease, in which abnormal transcription of synaptic genes and metabolic disturbance not related to transcription may drive white matter loss.