Whose Rebellion? Reformed Resistance Theory in America: Part I

Students of the American Founding routinely assert that America\u27s civic leaders were influenced by secular Lockean political ideas, especially on the question of resistance to tyrannical authority. Yet virtually every political idea usually attributed to John Locke was alive and well among Reformed political thinkers decades before Locke wrote the Second Treatise. In this two-part essay, we trace just one element of the Reformed political tradition: the question of who may actively and justly resist a tyrant. We focus on the American experience but begin our discussion by considering the early Reformers

Whose Rebellion? Reformed Resistance Theory in America: Part II

Students of the American Founding routinely assert that America\u27s civic leaders were influenced by secular Lockean political ideas, especially on the question of resistance to tyrannical authority. In the first part of this series, we showed that virtually all Reformed writers, from Calvin to the end of the Glorious Revolution, agreed that tyrants could be actively resisted. The only debated question was who could resist them. In this essay, we contend that the Reformed approach to active resistance had an important influence on how America\u27s Founders responded to perceived tyrannical actions by Parliament and the Crown

Whose Rebellion? Reformed Resistance Theory in America: Part II

Students of the American Founding routinely assert that America\u27s civic leaders were influenced by secular Lockean political ideas, especially on the question of resistance to tyrannical authority. In the first part of this series, we showed that virtually all Reformed writers, from Calvin to the end of the Glorious Revolution, agreed that tyrants could be actively resisted. The only debated question was who could resist them. In this essay, we contend that the Reformed approach to active resistance had an important influence on how America\u27s Founders responded to perceived tyrannical actions by Parliament and the Crown

Histidine168 is crucial for ΔpH-dependent gating of the human voltage-gated proton channel, hHV1

We recently identified a voltage-gated proton channel gene in the snail Helisoma trivolvis, HtHV1, and determined its electrophysiological properties. Consistent with early studies of proton currents in snail neurons, HtHV1 opens rapidly, but it unexpectedly exhibits uniquely defective sensitivity to intracellular pH (pHi). The H+ conductance (gH)-V relationship in the voltage-gated proton channel (HV1) from other species shifts 40 mV when either pHi or pHo (extracellular pH) is changed by 1 unit. This property, called ΔpH-dependent gating, is crucial to the functions of HV1 in many species and in numerous human tissues. The HtHV1 channel exhibits normal pHo dependence but anomalously weak pHi dependence. In this study, we show that a single point mutation in human hHV1—changing His168 to Gln168, the corresponding residue in HtHV1—compromises the pHi dependence of gating in the human channel so that it recapitulates the HtHV1 response. This location was previously identified as a contributor to the rapid gating kinetics of HV1 in Strongylocentrotus purpuratus. His168 mutation in human HV1 accelerates activation but accounts for only a fraction of the species difference. H168Q, H168S, or H168T mutants exhibit normal pHo dependence, but changing pHi shifts the gH-V relationship on average by /unit. Thus, His168 is critical to pHi sensing in hHV1. His168, located at the inner end of the pore on the S3 transmembrane helix, is the first residue identified in HV1 that significantly impairs pH sensing when mutated. Because pHo dependence remains intact, the selective erosion of pHi dependence supports the idea that there are distinct internal and external pH sensors. Although His168 may itself be a pHi sensor, the converse mutation, Q229H, does not normalize the pHi sensitivity of the HtHV1 channel. We hypothesize that the imidazole group of His168 interacts with nearby Phe165 or other parts of hHV1 to transduce pHi into shifts of voltage-dependent gating

ISCAN: a System for Integrated Phonetic Analyses Across Speech Corpora

Speech corpora of many languages, styles, and formats exist in the world, representing significant potential for the phonetic sciences. However in practice there are significant practical and methodological barriers to conducting the “same study” across corpora, including necessary technical skills and non-comparability of results using non-standardized measures. We introduce an open-source software system for Integrated Speech Corpus ANalysis (ISCAN), which enables automated acoustic phonetic analysis across spoken corpora of diverse formats and sizes. A web-browser-based GUI and Python package allow for different user backgrounds. The system is a major update of core functionality for fully- automated speech corpus analysis (importing, enriching, querying) from a previous version, to meet new goals: different user configurations, working with restricted datasets, and interacting with data (visualization and correction). The system’s flexibility for different projects is shown in two use cases: large-scale automatic segmental analysis of spontaneous speech across English dialects, and smallerscale semi-automatic prosodic analysis

Exotic Properties of a Voltage-gated Proton Channel from the Snail Helisoma trivolvis

Voltage-gated proton channels, HV1, were first reported in Helix aspersa snail neurons. These H+ channels open very rapidly, two to three orders of magnitude faster than mammalian HV1. Here we identify an HV1 gene in the snail Helisoma trivolvis and verify protein level expression by Western blotting of H. trivolvis brain lysate. Expressed in mammalian cells, HtHV1 currents in most respects resemble those described in other snails, including rapid activation, 476 times faster than hHV1 (human) at pHo 7, between 50 and 90 mV. In contrast to most HV1, activation of HtHV1 is exponential, suggesting first-order kinetics. However, the large gating charge of ∼5.5 e0 suggests that HtHV1 functions as a dimer, evidently with highly cooperative gating. HtHV1 opening is exquisitely sensitive to pHo, whereas closing is nearly independent of pHo. Zn2+ and Cd2+ inhibit HtHV1 currents in the micromolar range, slowing activation, shifting the proton conductance–voltage (gH-V) relationship to more positive potentials, and lowering the maximum conductance. This is consistent with HtHV1 possessing three of the four amino acids that coordinate Zn2+ in mammalian HV1. All known HV1 exhibit ΔpH-dependent gating that results in a 40-mV shift of the gH-V relationship for a unit change in either pHo or pHi. This property is crucial for all the functions of HV1 in many species and numerous human cells. The HtHV1 channel exhibits normal or supernormal pHo dependence, but weak pHi dependence. Under favorable conditions, this might result in the HtHV1 channel conducting inward currents and perhaps mediating a proton action potential. The anomalous ΔpH-dependent gating of HtHV1 channels suggests a structural basis for this important property, which is further explored in this issue (Cherny et al. 2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201711968)

The scope of safety in English older adult care homes: a qualitative analysis of Safeguarding Adult Reviews

Purpose: This paper aims to explore the content of Safeguarding Adult Reviews (SARs) from older adult care homes to understand how safety is understood and might be measured in practice. Design/methodology/approach: SARs relevant to older adult care homes from 2015 onwards were identified via the Social Care Institute of Excellence SARs library. Using thematic analysis, initial inductive coding was mapped to a health-derived safety framework, the Safety Measurement and Monitoring Framework (SMMF). Findings: The content of the SARs reflected the dimensions of the SMMF but gaining a deeper understanding of safety in older adult care homes requires additional understanding of how this unique context interacts with these dimensions to create and prevent risks and harms. This review identified the importance of external factors in care home safety. Originality/value: This study provides an insight into the scope of safety issues within care homes using the SARs content, and in doing so improves understanding of how it might be measured. The measurement of safety in care homes needs to acknowledge that there are factors external to care homes that a home may have little knowledge of and no ability to control

School-based physical activity intervention for older adolescents: rationale and study protocol for the Burn 2 Learn cluster randomised controlled trial

Introduction This trial aims to investigate the impact of a school-based physical activity programme, involving high-intensity interval training (HIIT), on the physical, mental and cognitive health of senior school students. Methods and analysis The Burn 2 Learn (B2L) intervention will be evaluated using a two-arm parallel group cluster randomised controlled trial with allocation occurring at the school level (to treatment or wait-list control). Schools will be recruited in two cohorts from New South Wales, Australia. The trial will aim to recruit ∼720 senior school students (aged 16-18 years) from 20 secondary schools (ie, 10 schools per cohort). A range of implementation strategies will be provided to teachers (eg, training, equipment and support) to facilitate the delivery of HIIT sessions during scheduled classes. In phase I and II (3 months each), teachers will facilitate the delivery of at least two HIIT sessions/week during lesson-time. In phase III (6 months), students will be encouraged to complete sessions outside of lesson-time (teachers may continue to facilitate the delivery of B2L sessions during lesson-time). Study outcomes will be assessed at baseline, 6 months (primary end point) and 12 months. Cardiorespiratory fitness (shuttle run test) is the primary outcome. Secondary outcomes include: vigorous physical activity, muscular fitness, cognition and mental health. A subsample of students will (i) provide hair samples to determine their accumulated exposure to stressful events and (ii) undergo multimodal MRI to examine brain structure and function. A process evaluation will be conducted (ie, recruitment, retention, attendance and programme satisfaction)

Process evaluation of a school-based high-intensity interval training program for older adolescents : the Burn 2 Learn cluster randomised controlled trial

Process evaluations can help to optimise the implementation of school-based physical activity interventions. The purpose of this paper is to describe the process evaluation of a school-based high-intensity interval training (HIIT) program for older adolescent students, known as Burn 2 Learn (B2L). B2L was evaluated via a cluster randomised controlled trial in 20 secondary schools (10 intervention, 10 control) in New South Wales, Australia. Teachers (n = 22 (55% female)) from the 10 intervention schools, delivered the program over three phases (Phases 1 and 2, 6 months; Phase 3, 6 months) to older adolescent students (n = 337 (50% female); mean ± standard deviation (SD) age = 16.0 ± 0.4 years). Process evaluation data were collected across the 12-month study period. Teachers delivered 2.0 ± 0.8 and 1.7 ± 0.6 sessions/week in Phases 1 and 2 respectively (mean total 25.9 ± 5.2), but only 0.6 ± 0.7 sessions/week in Phase 3. Observational data showed that session quality was high, however heart rate (HR) data indicated that only half of the students reached the prescribed threshold of ≥85% predicted HRmax during sessions. Over 80% of teachers reported they intended to deliver the B2L program to future student cohorts. Almost 70% of students indicated they intended to participate in HIIT in the future. Teachers considered the program to be adaptable, and both students and teachers were satisfied with the intervention. B2L was implemented with moderate-to-high fidelity in Phases 1 and 2, but low in Phase 3. Our findings add to the relatively scant process evaluation literature focused on the delivery of school-based physical activity programs