From Ruby-Red to Deep Purple: How New Hampshire Became a Top-Ten Swing State

New Hampshire has become a competitive swing state in presidential elections over the past two decades. Though New Hampshire was once a reliable red state and the home for many “Yankee Republicans,” the state has experienced a shift toward the Democratic Party beginning in the early 1990s. Scholars often attribute this shift to the “migration theory,” arguing that the influx of Massachusetts liberals who migrated to New Hampshire in the latter half of the twentieth century has created a larger Democratic voting bloc in the state. However, a county-level analysis of New Hampshire provides a different story. Southern urban counties with the highest migration rates, such as Hillsborough and Rockingham, had relatively small gains of Democratic voters and remain competitive swing counties. Northern rural counties with much lower migration rates, such as Coos and Grafton, have experienced a far greater political shift to the left. By using both of these case studies, this report casts doubt on the “migration theory” by showing that numerical migration rates do not fully account for New Hampshire’s shift. Instead, this report finds that the different types of economies in the southern and northern parts of New Hampshire significantly influence the political effects of migration in the state, offering a more nuanced theory based on county-level data than the one currently provided for the state as a whole

Multistable and multistep dynamics in neutrophil differentiation

BACKGROUND: Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. RESULTS: Here we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low (CD11b(Low)) and high (CD11b(High)) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" (CD11b(Low)) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate. CONCLUSION: These findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network

UK speech and language therapists’ assessment of children's expressive language, and functional impairment and impact, following the CATALISE publications

Background: In 2016/17, the CATALISE Consortium published the results of a multinational and multidisciplinary Delphi consensus study, representing agreement among professionals about the definition and process of identification of children with Developmental Language Disorder (DLD) (Bishop et al.,2016, 2017). The extent to which the current clinical practice of UK speech and language therapists (SLTs) reflects the CATALISE consensus statements is unknown. Aims: To investigate how UK SLTs’ expressive language assessment practicesreflect the CATALISE documents’ emphasis on the functional impairment andimpact caused by DLD, by examining: whether multiple sources of assess-ment information are gathered; how standardised and non-standardised sources are combined in clinical decision-making, and how clinical observation andlanguage sample analysis are utilised. Methods and Procedures: An anonymous, online survey was carried out between August 2019 and January 2020. It was open to UK-based paediatric SLTs who assess children up to age 12 with unexplained difficulties using language. Questions probed different aspects of expressive language assessment which are referred to in the CATALISE consensus statements and supplementary comments, and asked about participants’ familiarity with the CATALISE statements. Responses were analysed using simple descriptive statistics and content analysis. Outcomes and Results: The questionnaire was completed by 104 participants, from all four regions of the United Kingdom, working in a range of clinical settings with different levels of professional experience of DLD. The findings indicate that clinical assessment practices broadly align with the CATALISE statements. Although clinicians carry out standardised assessments more frequently than other types of assessment, they also gather information from other sources and use this alongside standardised test scores to inform clinical decisions. Clinical observation and language sample analysis are commonly utilised to evaluate functional impairment and impact, along with parent/carer/teacher and child report. However, asking about the child’s own perspective could be more widely utilised. The findings also highlight a lack of familiarity with the details of the CATALISE documents among two thirds of the participants. Conclusions and Implications: Assessment practices broadly align with the CATALISE statements, but there is a need for greater clarity regarding terminology and the assessment of functional language impairment and impact. This research should prompt discussion in the profession about how to further develop and adopt expressive language assessment practices which reflect the CATALISE consensus and support effective assessment

Towards Equity in Health: Researchers Take Stock.

For the 2016 end-of-the-year editorial, the PLOS Medicine editors asked 7 global health leaders to discuss developments relevant to the equitable provision of medical care to all populations. The result is a collection of expert views on ethical trial design, research during outbreaks, high-burden infectious diseases, diversity in research and protection of migrants

Pre and postoperative lactate levels and lactate clearance in predicting in-hospital mortality after surgery for gastrointestinal perforation

Abstract Background This study aimed to compare the prognostic significance of pre and postoperative lactate levels and postoperative lactate clearance in the prediction of in-hospital mortality after surgery for gastrointestinal (GI) perforation. Methods Among patients who underwent surgery for GI perforation between 2013 and 2017, only patients whose lactate were measured before and after surgery were included and divided into an in-hospital mortality group and a survival group. Data on demographics, comorbidities, pre and postoperative laboratory test results, and operative findings were collected. Risk factors for in-hospital mortality were identified, and receiver-operating characteristic (ROC) curve analysis was performed for pre and postoperative lactate levels and postoperative lactate clearance. Results Of 104 included patients, 17 patients (16.3%) died before discharge. The in-hospital mortality group demonstrated higher preoperative lactate (6.3 ± 5.1 vs. 3.5 ± 3.2, P = 0.013), SOFA score (4.5 ± 1.7 vs. 3.4 ± 2.3, P = 0.004), proportions of patients with lymphoma (23.5% vs. 2.3%, P = 0.006), and rates of contaminated ascites (94.1% vs. 68.2%, P = 0.036) and lower preoperative hemoglobin (10.4 ± 1.6 vs. 11.8 ± 2.4, P = 0.018) compare to the survival group. Multivariate analysis revealed that postoperative lactate (HR 1.259, 95% CI 1.084–1.463, P = 0.003) and preoperative hemoglobin (HR 0.707, 95% CI 0.520–0.959, P = 0.026) affected in-hospital mortality. In the ROC curve analysis, the largest area under the curve (AUC) was shown in the postoperative lactate level (AUC = 0.771, 95% CI 0.678–0.848). Conclusion Of perioperative lactate levels in patients underwent surgery for GI perforation, postoperative lactate was the strongest predictor for in-hospital mortality

Spatial mapping of hematopoietic clones in human bone marrow

UNLABELLED: Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., \u3e2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution of somatic mutations in the hematopoietic compartment, the restriction of somatic mutations to specific subpopulations of hematopoietic cells, and spatial constraints of these clones in the bone marrow. This proof of principle paves the way to answering fundamental questions regarding CH spatial organization and factors driving CH expansion and malignant transformation in the bone marrow. SIGNIFICANCE: CH occurs commonly in humans and can predispose to hematologic malignancy. Although well characterized in blood, it is poorly understood how clones are spatially distributed in the bone marrow. To answer this, we developed methods for spatially aware somatic mutation profiling to describe clonal heterogeneity in human bone marrow. See related commentary by Austin and Aifantis, p. 139

Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

<p>Abstract</p> <p>Background</p> <p>HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples.</p> <p>Results</p> <p>Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (<it>P </it>< 0.0001) and ATLL patients (<it>P </it>< 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (<it>P </it>< 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (<it>R </it>= 0.76), but not in HAM/TSP.</p> <p>Conclusion</p> <p>These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.</p

Changes in the incidence of cardiopulmonary resuscitation before and after implementation of the Life-Sustaining Treatment Decisions Act

Background The Life-Sustaining Treatment (LST) Decisions Act allows withholding and withdrawal of LST, including cardiopulmonary resuscitation (CPR). In the present study, the incidence of CPR before and after implementation of the Act was compared. Methods This was a retrospective review involving hospitalized patients who underwent CPR at a single center between February 2016 and January 2020 (pre-implementation period, February 2016 to January 2018; post-implementation period, February 2018 to January 2020). The primary outcome was monthly incidence of CPR per 1,000 admissions. The secondary outcomes were duration of CPR, return of spontaneous circulation (ROSC) rate, 24-hour survival rate, and survival-to-discharge rate. The study outcomes were compared before and after implementation of the Act. Results A total of 867 patients who underwent CPR was included in the analysis. The incidence of CPR per 1,000 admissions showed no significant difference before and after implementation of the Act (3.02±0.68 vs. 2.81±0.75, P=0.255). The ROSC rate (67.20±0.11 vs. 70.99±0.12, P=0.008) and survival to discharge rate (20.24±0.09 vs. 22.40±0.12, P=0.029) were higher after implementation of the Act than before implementation. Conclusions The incidence of CPR did not significantly change for 2 years after implementation of the Act. Further studies are needed to assess the changes in trends in the decisions of CPR and other LSTs in real-world practice