Current managerial practices and social trends are incentivizing an increase in citizen participation and government operational transparency and accountability. As a consequence, small to medium ...size cities have new opportunities for delivering services to their citizens in a more effective and efficient manner. However, in many cases, the technology capabilities of these cities and their IT staffing are not adequate. Starting at the top, most small-to-medium size cities do not have a Chief Information Officer (CIO). Instead, they have appointed officials with a wide variety of titles ranging from IT Director, IS Manager to IT Specialist among others. These officials face the problem of building operational capabilities at the same time that they develop a strategic vision for their organizations. In this paper, we look at the perceptions of local-level officials responsible for the operation of IT across New York State, about their own role and challenges in this transition from an operational to a strategic focus. Our results suggest that giving IT leadership a broader role and higher responsibilities could result in value for both government and citizens.
This paper sets out good practice for clinicians involved in interpreting variant reports for patients with inherited bleeding disorders. It is aimed primarily at doctors, nurses and allied ...healthcare professionals who may not have had specific training in genetic testing methodology or reporting. It deals with uncertainty in classification of variant pathogenicity and the handling of incidental findings.
Analysis of short tandem repeats (STRs) using capillary electrophoresis (CE) is the current standard for forensic DNA analysis. However, massively parallel sequencing (MPS) of STRs has the potential ...to provide greater discriminating power through the use of sequence-defined alleles. By determining the base pair sequence of an STR, alleles of the same length may be differentiated. The ForenSeqTM MainstAY Kit from Verogen is an MPS kit designed to analyze forensically relevant samples on the Illumina MiSeq FGxTM System. To assess the ForenSeqTM MainstAY Kit’s ability to analyze evidence found in forensic casework, samples were selected from a set of differential extraction samples from a previous study. The samples had been extracted using either the Qiagen EZ1® DNA Investigator® Kit or a Temperature Controlled Differential Extraction (TCDE) method and analyzed using CE. The selected samples were prepared with the ForenSeqTM MainstAY Kit in 2 replicates, along with a dilution series to assess the sensitivity of the kit. The results showed that the ForenSeqTM MainstAY Kit was able to produce profiles of similar quality for forensic comparison to CE. Although read counts were lower than expected at some concentrations, at least one of the dilution series replicates produced a full profile at concentrations as low as 0.4 ng. Total read count per locus varied, with the PentaD and PentaE loci producing the lowest mean read counts. Heterozygote balance between sequencing replicates was consistent. However, CE did display better heterozygote balance than MPS. Most importantly, isoalleles were detected at the D21S11, D8S1179, D9S1122, D3S1358, and D13S317 loci and could be used to determine the genotypes at a locus with two contributors. Overall, the ForenSeqTM MainstAY Kit could be a valuable asset to the field of forensic DNA analysis for its ability to distinguish alleles by sequence as well as by length.
Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin–angiotensin ...system. Cardiac renin–angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin–angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague–Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3–P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin–angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions.
Background
Preterm birth (< 37 weeks of gestation) occurs in approximately 10% of births worldwide; the majority of preterm births are moderately preterm (between 32 and 36 weeks gestation). We ...hypothesized that when birth occurs before term the major conduit arteries would be structurally and functionally immature and thus ill‐prepared for the hemodynamic transition that necessarily occurs at birth. Utilising a preclinical sheep model, our aims were to compare the structure and function of the thoracic aorta and common carotid arteries of moderately preterm (0.9 of gestation) and term‐born lambs in the immediate period after birth, and to determine whether there was upregulation of vascular injury‐associated genes following moderate preterm birth.
Methods
Time‐mated ewes were induced to vaginally deliver lambs either preterm (132 ± 1 days of gestation; n=11 females and n=10 males) or at term (147 ± 1 days of gestation; n=10 females and n=5 males). At 2 days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries and right and left common carotid arteries was conducted in anaesthetised lambs. The lambs were then euthanized and segments of the thoracic aorta and left common carotid artery were either snap frozen for later real‐time PCR analyses or immersion‐fixed in 10% buffered formalin for histological quantification of collagen, smooth muscle and elastin within the medial layer.
Results
Overall there were few differences in vascular structure, wall composition and blood flow measurements of large conduit arteries at postnatal day 2 between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males; p=0.048), narrowing of the carotid arteries (p=0.004) and a reduction in peak aortic systolic blood flow (p=0.049); all of which have the potential to impact on cardiovascular function if they persist long‐term. In addition, there was significantly increased mRNA expression of the cell adhesion marker P‐selectin in the thoracic aortic wall (p=0.001) and the pro‐inflammatory marker IL‐1β in the left carotid artery (p=0.04) in preterm lambs, suggestive of postnatal vascular injury.
Conclusions
The findings suggest that offspring born moderately preterm may be at increased risk of cardiovascular impairment later in life.
Support or Funding Information
This study was funded by the National Health and Medical Research Council of Australia
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Most studies about cross-boundary information sharing (CBIS) focus on private or public sector organizations only. There is limited research within regulated environments, which often requires ...information to be shared among multiple public, private and nonprofit organizations. This paper explores CBIS in different regulatory contexts, with a focus on financial markets in the USA, and finds some unique characteristics in terms of information asymmetries, incentive and governance structures, and structural complexity.
While the importance and success factors of information sharing has been widely discussed between businesses within the industry, the knowledge gap between the regulator and the regulated has remained unexplored. The purpose of this paper is to help practitioners understand what prevents effective information sharing between the regulated and regulator, and among the regulators, given the unique socio-technological environment they are in. We developed an understanding of regulatory challenges of effectively monitoring market activities and mitigating systemic risk in the US financial market in relation to the cross-boundary information sharing challenges in various regulatory contexts
Abstract only Endothelial colony-forming cell (ECFC), a subtype of endothelial progenitor cells with high clonogenic and proliferative capacity, is present in cord and peripheral blood, participating ...in neovessel formation and regeneration. Cord blood ECFCs have impaired bioactivity in pregnancy complications and preterm (PT) birth. Dysfunction of cord blood ECFC is also related to complications of prematurity such as bronchopulmonary dysplasia. Although cardiovascular alterations, such as high blood pressure (BP) and left ventricular (LV) dysfunction, occur in PT subjects during adulthood, whether ECFC dysfunction beyond the neonatal period relates to such alterations is not known. OBJECTIVE: We aim in this study to assess if ECFC function relates to cardiovascular alterations in PT born adults. METHODS: Peripheral blood mononuclear cells from 30 young adults (21-28 years old) born very PT (<29 weeks gestation) and 30 at term (T, ≥37 weeks gestation) were separated by density gradient and cultured to ECFC colony formation. ECFC proliferative and angiogenic function were assessed in vitro by modified thymidine analogue (EdU) incorporation and tube formation in Matrigel. BP was measured by 24h monitor and LV mass index (g/cm 2 ) by ultrasound imaging. All analyses were performed blind; correlations were significant when p<0.05. RESULTS: The proportion of early (<15 days) and late (≥15 days) time for ECFC colony formation was different between PT and T, with a higher frequency for late growth or no colony in the PT born group. Time to colony formation inversely correlated with ECFC proliferation rate (r=-0.57, r 2 =0.32) and tube formation (r=-0.57, r 2 =0.33) in PT, which shows ECFC dysfunction in those PT subjects with late colony formation, with no significant correlations in T. Additionally, time to colony formation has positively related to systolic BP (r=0.54, r 2 =0.29) and LV mass index (r=0.49, r 2 =0.24) in PT born subjects. CONCLUSION: Our findings demonstrate, for the first time, an association between dysfunctional circulating ECFCs and cardiovascular alterations in adults born PT. We also show that ECFC dysfunction, in PT adults, significantly relates to important cardiovascular risk factors such as high BP and increased LV mass.
IntroductionAmong subtypes of endothelial progenitor cells, endothelial colony-forming cells (ECFC) display high proliferative and angiogenic capacity in vitro and are considered biomarkers of ...angiogenic/regenerative capacity. Cord blood ECFC from preterm born (PT) infants have impaired bioactivity, especially in those who develop prematurity-related complications such as bronchopulmonary dysplasia. Whether ECFC dysfunction persists in PT beyond the neonatal period is not known.ObjectiveOur aim was to assess ECFC bioactivity (in vitro growth, angiogenic capacity) in extremely PT vs. term (T) born young adults.MethodsECFC were obtained from peripheral blood from 19 young adults (21-28 years old) born extremely PT (<29 weeks gestation) and 19 T (≥37 weeks, paired by gender, age and socioeconomic status). Mononuclear cells (PBMC) were separated by density gradient and plated (5x10(6) cells/flask) to allow ECFC colony formation. ECFC were cultured to assess cell phenotype (CD45-/CD34+/CD31+/KDR+), in vitro proliferation rate by modified thymidine analogue EdU incorporation, and tubular formation in Matrigel.ResultsECFC colonies were obtained from 9 PT (48%) and 12 T (63%). The frequency distribution of the number of days to first colony formation was significantly different in PT vs. T, with higher frequency of late (> 15 days) and absence of any colony formation in PT (p=0.033). In PT, days to form 1st ECFC colony inversely correlated with ECFC proliferation rate (r=-0.85, p<0.001), and angiogenic capacity shown as number of tubes (r=-0.72, p=0.037) and branches (r=-0.68, p=0.043) formed in Matrigel, whereas in T these correlations were not significant with similar ECFC function at any time of colony formation. In PT, tubular formation negatively correlated with neonatal length of hospital stay (r=-0.72, p=0.03), a proxy of prematurity-related complications.ConclusionsTime to first ECFC colony formation, proliferation rate and in vitro tubular formation are significantly altered in PT vs. T young adults. Overall data suggests that extremely PT born young adults display impaired ECFC bioactivity, which may contribute to the development of cardiovascular diseases associated with impaired angiogenesis in this population.
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