Modulation of human corticospinal excitability by paired associative stimulation

Paired Associative Stimulation (PAS) has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS) delivered to the contralateral primary motor cortex (M1). Repeated pairing of the stimuli (i.e., association) over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI). It has been suggested that these effects represent a form of associative long-term potentiation (LTP) and depression (LTD) that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasizing the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation

CLASSnmat: A global night marine air temperature data set, 1880–2019

A new data set of Night Marine Air Temperature (NMAT) is presented that builds on the HadNMAT2 data set, which was released in 2013. In a similar manner to HadNMAT2, the new data set (CLASSnmat) provides uninterpolated, monthly global values at a 5° resolution back to 1880. In addition to being extended to the end of 2019, four main developments are made in CLASSnmat: (1) the NMAT values are extracted from the most recent version of the International Comprehensive Ocean‐Atmosphere Data Set (ICOADS Release 3) and a revised method of eliminating duplicated observations is used; (2) values of NMAT are adjusted to 2m and 20m heights in addition to the 10 m height used in HadNMAT2; (3) a refinement is made to the corrections necessary during World War 2, which uses more of the NMAT observations and hence results in a more extensive spatial coverage for this period than was possible in HadNMAT2; (4) an updated gridding method is used that allows for an improved propagation of uncertainty from the individual NMAT values through to the gridded estimates. In this paper, the method used to construct CLASSnmat (version 1.0.0.0) is described

Area distribution of the planar random loop boundary

We numerically investigate the area statistics of the outer boundary of planar random loops, on the square and triangular lattices. Our Monte Carlo simulations suggest that the underlying limit distribution is the Airy distribution, which was recently found to appear also as area distribution in the model of self-avoiding loops.Comment: 10 pages, 2 figures. v2: minor changes, version as publishe

Metal-Poor Stars Observed with the Magellan Telescope I. Constraints on Progenitor Mass and Metallicity of AGB Stars Undergoing s-Process Nucleosynthesis

We present a comprehensive abundance analysis of two newly-discovered carbon-enhanced metal-poor (CEMP) stars. HE2138-3336 is a s-process-rich star with [Fe/H] = -2.79, and has the highest [Pb/Fe] abundance ratio measured thus far, if NLTE corrections are included ([Pb/Fe] = +3.84). HE2258-6358, with [Fe/H] = -2.67, exhibits enrichments in both s- and r-process elements. These stars were selected from a sample of candidate metal-poor stars from the Hamburg/ESO objective-prism survey, and followed up with medium-resolution (R ~ 2,000) spectroscopy with GEMINI/GMOS. We report here on derived abundances (or limits) for a total of 34 elements in each star, based on high-resolution (R ~ 30,000) spectroscopy obtained with Magellan-Clay/MIKE. Our results are compared to predictions from new theoretical AGB nucleosynthesis models of 1.3 Mo with [Fe/H] = -2.5 and -2.8, as well as to a set of AGB models of 1.0 to 6.0 Mo at [Fe/H] = -2.3. The agreement with the model predictions suggests that the neutron-capture material in HE2138-3336 originated from mass transfer from a binary companion star that previously went through the AGB phase, whereas for HE2258-6358, an additional process has to be taken into account to explain its abundance pattern. We find that a narrow range of progenitor masses (1.0 < M(Mo) < 1.3) and metallicities (-2.8 < [Fe/H] < -2.5) yield the best agreement with our observed elemental abundance patterns.Comment: Accepted for publication in Ap

Leptospirosis and an Animal Bite

In October 2013, leptospirosis was identified in a 20-year-old male. The male was bitten on his hand by either his canine or a skunk while breaking up a fight between the two animals. Eight days after the bite, the male developed fever, headache, drowsiness, neck pain, nausea, vomiting, diarrhea, malaise and erythematous rash. Diagnosis was confirmed by amplification of Leptospira by DNA from a urine specimen. Veterinarian serology testing of the canine for Leptospira was negative. Leptospira in a human, acquired from an animal bite is a rare occurrence

CHK1 inhibition as a strategy for targeting fanconi anemia (FA) DNA repair pathway deficient tumors

<p>Abstract</p> <p>Background</p> <p>DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyper-dependent on DNA damage response pathways, including the CHK1-kinase-mediated response. These observations suggest that DNA repair deficient tumors should exhibit increased sensitivity to CHK1 inhibition. Here we offer experimental evidence in support of this hypothesis.</p> <p>Results</p> <p>Using isogenic pairs of cell lines differing only in the Fanconi Anemia (FA) DNA repair pathway, we showed that FA deficient cell lines were hypersensitive to <it>CHK1 </it>silencing by independent siRNAs as well as CHK1 pharmacologic inhibition by Gö6976 and UCN-01. In parallel, an siRNA screen designed to identify gene silencings synthetically lethal with CHK1 inhibition identified genes required for FA pathway function. To confirm these findings <it>in vivo</it>, we demonstrated that whole zebrafish embryos, depleted for <it>FANCD2 </it>by a morpholino approach, were hypersensitive to Gö6976. Silencing of FA genes led to hyper-activation of CHK1 and vice versa. Furthermore, inactivation of CHK1 in FA deficient cell lines caused increased accumulation of DNA strand and chromosomal breakages. These results suggest that the functions subserved by CHK1 and the FA pathway mutually compensate in maintaining genome integrity. As CHK1 inhibition has been under clinical trial in combination with cisplatin, we showed that the FA specific tumoricidal effect of CHK1 inhibition and cisplatin was synergistic.</p> <p>Conclusion</p> <p>Taken together, these results suggest CHK1 inhibition as a strategy for targeting FA deficient tumors.</p

Does Job Stability Mediate the Relationship Between Intimate Partner Violence and Mental Health Among Low‐Income Women?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100283/1/ajop12053.pd

“A question of trust” and “a leap of faith”-study participants' perspectives on consent, privacy, and trust in smart home research:Qualitative study

BACKGROUND: Ubiquitous, smart technology has the potential to assist humans in numerous ways, including with health and social care. COVID-19 has notably hastened the move to remotely delivering many health services. A variety of stakeholders are involved in the process of developing technology. Where stakeholders are research participants, this poses practical and ethical challenges, particularly if the research is conducted in people’s homes. Researchers must observe prima facie ethical obligations linked to participants’ interests in having their autonomy and privacy respected. OBJECTIVE: This study aims to explore the ethical considerations around consent, privacy, anonymization, and data sharing with participants involved in SPHERE (Sensor Platform for Healthcare in a Residential Environment), a project for developing smart technology for monitoring health behaviors at home. Participants’ unique insights from being part of this unusual experiment offer valuable perspectives on how to properly approach informed consent for similar smart home research in the future. METHODS: Semistructured qualitative interviews were conducted with 7 households (16 individual participants) recruited from SPHERE. Purposive sampling was used to invite participants from a range of household types and ages. Interviews were conducted in participants’ homes or on-site at the University of Bristol. Interviews were digitally recorded, transcribed verbatim, and analyzed using an inductive thematic approach. RESULTS: Four themes were identified—motivation for participating; transparency, understanding, and consent; privacy, anonymity, and data use; and trust in research. Motivations to participate in SPHERE stemmed from an altruistic desire to support research directed toward the public good. Participants were satisfied with the consent process despite reporting some difficulties—recalling and understanding the information received, the timing and amount of information provision, and sometimes finding the information to be abstract. Participants were satisfied that privacy was assured and judged that the goals of the research compensated for threats to privacy. Participants trusted SPHERE. The factors that were relevant to developing and maintaining this trust were the trustworthiness of the research team, the provision of necessary information, participants’ control over their participation, and positive prior experiences of research involvement. CONCLUSIONS: This study offers valuable insights into the perspectives of participants in smart home research on important ethical considerations around consent and privacy. The findings may have practical implications for future research regarding the types of information researchers should convey, the extent to which anonymity can be assured, and the long-term duty of care owed to the participants who place trust in researchers not only on the basis of this information but also because of their institutional affiliation. This study highlights important ethical implications. Although autonomy matters, trust appears to matter the most. Therefore, researchers should be alert to the need to foster and maintain trust, particularly as failing to do so might have deleterious effects on future research