Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.     

Calculating small-angle scattering intensity functions from electron-microscopy images

We outline procedures to calculate small-angle scattering (SAS) intensity functions from 2-dimensional electron-microscopy (EM) images. Two types of scattering systems were considered: (a) the sample is a set of particles confined to a plane; or (b) the sample is modelled as parallel, infinitely long cylinders that extend into the image plane. In each case, an EM image is segmented into particle instances and the background, whereby coordinates and morphological parameters are computed and used to calculate the constituents of the SAS-intensity function. We compare our results with experimental SAS data, discuss limitations, both general and case specific, and outline some applications of this method which could potentially complement experimental SAS.

We outline procedures to calculate small-angle scattering (SAS) intensity functions from 2-dimensional electron-microscopy (EM) images for two types of scattering systems.

The structures of nanoparticulate systems are commonly characterized by various forms of electron microscopy (EM) and small-angle scattering (SAS) methods. The size and shape of nanoparticles, as well as their spatial-distribution functions, are of particular interest since they govern their structure–function relationships and thus their nanotechnological prospects.^1–6 EM and SAS data are highly complementary. For example, the former images a specific section of a nanomaterial, while the latter realizes its bulk structure by averaging signals obtained from a larger overall area and depth reflective of the sample thickness and beam size. There exists a high degree of overlap in the length scale that is interrogated by EM and SAS data on the same nanomaterial. Yet, these data are necessarily acquired separately and they are analyzed independently. Nevertheless, if suitably processed, the data from one metrology could be used to reconstruct the other. This could draw out the maximum possible structural information about a nanomaterial, or allow data from both sources to be fused to obtain more accurate insights or even highlight processes that result in discrepancies between data from the two methods.This work presents two case studies in which we calculate SAS data from 2-D EM images where (1) the particles being characterized exist on a plane; (2) the sample being imaged can be modelled as parallel, infinitely long cylinders that extend into the image plane. In both cases, we discuss limitations that result in discrepancies between image-obtained SAS intensities and those obtained experimentally. Despite these limitations, we discuss how this method can be complementary to small-angle scattering measurements, by informing experimental design decisions and aiding in model selection. The second case that we present was partially explored by Worthington and Inouye,⁷ and later Meek and Quantock⁸ as well as Quantock et al.⁹ They studied the interfibril distance of collagen fibres in animal corneas by calculating an interference function from pairwise distances of points obtained from an EM image. Their interference function is related to the structure factor which we include in our calculation of SAS intensities, along with form factors which we additionally compute from images. Grubb et al.¹⁰ studied the effect of the orientation of lamellar stack structures on SAXS patterns. The authors did this by generating synthetic images of arrays of lamellar stacks and simulating SAXS data using the 2-D Fourier transform, where they use the Fourier Slice theorem to obtain a 2-D slice of the 3-D transform.¹¹ Afsari et al.¹² and Kim et al.¹³ outline a procedure for calculating small-angle X-ray scattering (SAXS) data from cryo-EM images. Their work makes use of the fact that averaging the correlation functions of many cryo-EM images is equivalent to the Abel transform of SAXS data. Their work is complementary to ours as both methods can be applied under different circumstances. Our work is relevant in situations where image-processing and computer-vision techniques can be employed to segment single EM images and determine morphological and structural information about the scatterers; theirs is relevant when one has numerous cryo-EM images of the same sample.     

Improving diversity in study participation: Patient perspectives on barriers,racial differences and the role of communities

IntroductionThe lack of racial/ethnic diversity in research potentially limits the generalizability of findings to a broader population, highlighting the need for greater diversity and inclusion in clinical research. Qualitative research (i.e., focus groups) was conducted to identify (i) the potential motivators and barriers to study participation across different races and ethnicities; (ii) preferred delivery of education and information to support healthcare decision‐making and the role of the community.MethodsPatient focus groups were conducted with 26 participants from the sponsor''s Patient Engagement Research Councils selected through subjective sampling. Recruitment prioritized adequate representation across different race/ethnic groups. Participation was voluntary and participants underwent a confidential interview process before selection. Narrative analysis was used to identify themes and draw insights from interactions. Experienced research specialists identified emerging concepts, and these were tested against new observations. The frequency of each concept was examined to understand its importance.ResultsBased on self‐selected race/ethnicity, participants were divided into five focus groups (Groups: African American/Black: 2; Hispanic/Latino, Asian American, and white: 1 each) and were asked to share their experiences/opinions regarding the stated objectives. Barriers to study participation included: limited awareness of opportunities to participate in research, fears about changes in standard therapy, breaking cultural norms/stigma, religion‐related concerns and mistrust of clinical research. Participants identified the importance of transparency by pharmaceutical companies and other entities to build trust and partnership and cited key roles that communities can play. The perceptions of the African American group regarding diversity/inclusion in research studies appeared to be different from other groups; a lack of trust in healthcare providers, concerns about historical instances of research abuse and the importance of prayer were cited.ConclusionThis study provided insights into barriers to study participation, and also highlighted the need for pharmaceutical companies and other entities to authentically engage in strategies that build trust within communities to enhance recruitment among diverse populations.Patient or Public ContributionThe data collected in the present study was provided by the participants in the focus groups.     

Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia

Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design.     

Analytical validation of anti-toxoplasma IgG immunoassays

There are often discrepancies when using different methods to measure anti-Toxoplasma gondii IgG levels in patient samples. The diagnostic performance of a chemiluminescent immunoassay (CLIA) and an enzyme-linked fluorescent assay (ELFA) used as confirmatory tests for samples identified as positive or equivocal by an electrochemiluminescent immunoassay (ECLIA) were examined. Cut-off values were those stated by the manufacturer, and Western blot was used to confirm the results of all methods. All samples identified as positive by ECLIA (n = 93) were confirmed as positive by Western blot, as were 14 of the 28 samples identified as equivocal. When these 121 samples were retested, the sensitivities of CLIA and ELFA were 64.4% and 73.8%, respectively. Both methods exhibited a specificity of 100%. This study confirms that the results obtained from the different immunoassays are not comparable, and neither CLIA nor ELFA should be used to confirm ECLIA results, which should instead be confirmed by methods such as Western blot or Sabin-Feldman dye test.     

Transitional Care Coordination in New York City Jails: Facilitating Linkages to Care for People with HIV Returning Home from Rikers Island

New York City (NYC) jails are the epicenter of an epidemic that overwhelmingly affects Black and Hispanic men and offer a significant opportunity for public health intervention. The NYC Department of Health and Mental Hygiene instituted population based approaches to identify the HIV-infected, initiate discharge planning at jail admission, and facilitate post-release linkages to primary care. Using a caring and supportive ‘warm transitions’ approach, transitional care services are integral to continuity of care. Since 2010, over three-quarters of known HIV-infected inmates admitted to jails received discharge plans; 74 % of those released were linked to primary care. The EnhanceLink initiative’s new Health Liaison, a lynchpin role, facilitated 250 court-led placements in medical alternatives to incarceration. Transitional care coordination programs are critical to facilitate continuity of care for people with chronic health conditions including the HIV-infected returning home from jail and for the public health of the communities to which they return.