Skill in Interpersonal Networks.

I study the cognitive and behavioral skills that people use to navigate social networks at work, via three separate but related papers. Paper 1 argues that relational schemas, which are the cognitive schemas that people use to guide interactions with other people (Baldwin 1992), are developed over time through exposure to others. However, having a lower variety of schemas (employing generic schemas for multiple relationships) enables a person to interact with more people using fewer cognitive resources (Abelson 1981), but having a greater variety of schemas (having unique schemas for each relation) enables a person to better adapt to the needs of each relationship. Using in-depth interviews, network data, and interaction data from an administrative department of a manufacturing organization, I find a curvilinear relationship between both social experience and network contacts in an environment and the degree to which people develop more specific relational schemas, providing evidence for this tension between the need to adapt to each relationship versus the constraint of cognitive overload. Paper 2 argues that social network position cannot precisely measure access to information flows in a social context. I develop a new method for measuring access to information, using time-ordered communication/interaction data, which accounts for the temporal ordering of communication and the constraints of time, scheduling, and other factors that cause variation in the frequency of communication across and within relationships. Paper 3 focuses on relational acumen, the ability to accurately perceive the strength of one’s relationships. Relational acumen is a form of network perception accuracy, a cognitive skill that provides a basis of power in organizations (Krackhardt 1990). I argue that people who have higher access to social information flows have greater relational acumen. Using data from the same organization, I find that network brokers have greater relational acumen – they are more accurate in perceiving their strong ties. More importantly, I find that having interactions that are in the midst of others’ interactions throughout the day (what I call “interaction efficiency”) provides the greatest benefit for relational acumen. Thus, how one interacts with contacts matters more than who one’s contacts are.PHDBusiness Administration and SociologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99782/1/ncotton_1.pd

A Census of Early Phase High-Mass Star Formation in the Central Molecular Zone

We present new observations of C-band continuum emission and masers to assess high-mass ($>$8 $M_\odot$) star formation at early evolutionary phases in the inner 200 pc of the Central Molecular Zone (CMZ) of the Galaxy. The continuum observation is complete to free-free emission from stars above 10-11 $M_\odot$ in 91% of the covered area. We identify 104 compact sources in the continuum emission, among which five are confirmed ultracompact H II regions, 12 are candidates of ultra-compact H II regions, and the remaining 87 sources are mostly massive stars in clusters, field stars, evolved stars, pulsars, extragalactic sources, or of unknown nature that is to be investigated. We detect class II CH$_3$OH masers at 23 positions, among which six are new detections. We confirm six known H$_2$CO masers in two high-mass star forming regions, and detect two new H$_2$CO masers toward the Sgr C cloud, making it the ninth region in the Galaxy that contains masers of this type. In spite of these detections, we find that current high-mass star formation in the inner CMZ is only taking place in seven isolated clouds. The results suggest that star formation at early evolutionary phases in the CMZ is about 10 times less efficient than expected by the dense gas star formation relation, which is in line with previous studies that focus on more evolved phases of star formation. This means that if there will be any impending, next burst of star formation in the CMZ, it has not yet begun

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda

Abstract Background: The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda. Methods: The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors. Results: In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions. Conclusion: The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Evaluation of both exonic and intronic variants for effects on RNA splicing allows for accurate assessment of the effectiveness of precision therapies.

Elucidating the functional consequence of molecular defects underlying genetic diseases enables appropriate design of therapeutic options. Treatment of cystic fibrosis (CF) is an exemplar of this paradigm as the development of CFTR modulator therapies has allowed for targeted and effective treatment of individuals harboring specific genetic variants. However, the mechanism of these drugs limits effectiveness to particular classes of variants that allow production of CFTR protein. Thus, assessment of the molecular mechanism of individual variants is imperative for proper assignment of these precision therapies. This is particularly important when considering variants that affect pre-mRNA splicing, thus limiting success of the existing protein-targeted therapies. Variants affecting splicing can occur throughout exons and introns and the complexity of the process of splicing lends itself to a variety of outcomes, both at the RNA and protein levels, further complicating assessment of disease liability and modulator response. To investigate the scope of this challenge, we evaluated splicing and downstream effects of 52 naturally occurring CFTR variants (exonic = 15, intronic = 37). Expression of constructs containing select CFTR intronic sequences and complete CFTR exonic sequences in cell line models allowed for assessment of RNA and protein-level effects on an allele by allele basis. Characterization of primary nasal epithelial cells obtained from individuals harboring splice variants corroborated in vitro data. Notably, we identified exonic variants that result in complete missplicing and thus a lack of modulator response (e.g. c.2908G>A, c.523A>G), as well as intronic variants that respond to modulators due to the presence of residual normally spliced transcript (e.g. c.4242+2T>C, c.3717+40A>G). Overall, our data reveals diverse molecular outcomes amongst both exonic and intronic variants emphasizing the need to delineate RNA, protein, and functional effects of each variant in order to accurately assign precision therapies