Collaboration in inter-organizational networks is a major driver of innovation. Nevertheless, methods that practitioners can rely upon for managing innovation networks are still scarce. This research ...fills this gap by providing an approach that increases innovation output by intensifying collaboration in networks. An action research methodology with two cycles of action was adopted. The first cycle develops a method of network assessment designed to evaluate a network’s collaboration potential. The second cycle iteratively builds on the first cycle and extends the method by a managerial approach to network management on an individual level.
ObjectiveTo evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120 mg/month) and pegvisomant (40–120 mg/week) in acromegaly.DesignThis is a 28-week, multicenter, open-label, ...single-arm sequential study.MethodsPatients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120 mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on IGF1 levels to 40–80 mg once weekly or 40 or 60 mg twice weekly).ResultsIn total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60 mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P<0.0001) with median pegvisomant dose at 60 mg/week. Being nondiabetic (odds ratio (OR): 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (−0.6±1.6) and soft tissue swelling (−0.6±1.8). Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment related – thrombocytopenia, urticaria; not treatment related – abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to >5×upper limit of normal with normalization after withdrawal).ConclusionsIn patients partially controlled by SSAs, LA (120 mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60 mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.
Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater ...risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset.
We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses.
Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset.
Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.
ObjectiveIn primary aldosteronism, adrenal venous sampling (AVS) is essential for subtype differentiation as it evaluates aldosterone secretion from both adrenals. Selectivity of adrenal sampling is ...assessed by the ratio of cortisol concentrations in adrenal venous blood and inferior vena cava blood (Cadrenal/Civc). Since the criteria for selective adrenal sampling differ among the reported literature, we performed a study to evaluate the influence of different selectivity criteria on AVS results.Design and methodsReports of AVS were screened retrospectively. All AVS were performed with cosyntrophin infusion. Reports containing samples with Cadrenal/Civc≥10 taken from both adrenals and at least one other adrenal sample characterised by Cadrenal/Civc≥1.1 were enrolled. For each individual, we chose reference samples that were defined by the highest Cadrenal/Civc achieved from each adrenal. The significance of the remaining samples with Cadrenal/Civc≥1.1 was analysed in regard to their respective reference samples. We assessed the impact of analysed samples on identification of lateralisation of aldosterone secretion that is crucial for decisions concerning adrenalectomy.ResultsAVS reports of 87 patients were enrolled. A total of 225 adrenal samples were analysed and divided into five groups according to Cadrenal/Civc:1.1–1.99, 2–2.99, 3–4.99, 5–9.99 and ≥10. By comparing reference with analysed samples, a concordant assessment with respect to lateralisation of aldosterone secretion was observed in 39, 52, 72, 85 and 94% of the respective groups of analysed samples.ConclusionAVS provides consistent information when adrenal samples with high cortisol concentrations are used.
Context:
International comparisons of the health of mothers and babies provide essential benchmarks for guiding health practice and policy, but statistics are not routinely compiled in a comparable ...way. These data are especially critical during health emergencies, such as the coronavirus disease (COVID-19) pandemic. The Population Health Information Research Infrastructure (PHIRI) project aimed to promote the exchange of population data in Europe and included a Use Case on perinatal health.
Objective
: To develop and test a protocol for federated analysis of population birth data in Europe.
Methods:
The Euro-Peristat network with participants from 31 countries developed a Common Data Model (CDM) and R scripts to exchange and analyse aggregated data on perinatal indicators. Building on recommended Euro-Peristat indicators, complemented by a three-round consensus process, the network specified variables for a CDM and common outputs. The protocol was tested using routine birth data for 2015 to 2020; a survey was conducted assessing data provider experiences and opinions.
Results:
The CDM included 17 core data items for the testing phase and 18 for a future expanded phase. 28 countries and the four UK nations created individual person-level databases and ran R scripts to produce anonymous aggregate tables. Seven had all core items, 17 had 13-16, while eight had ≤12. Limitations were not having all items in the same database, required for this protocol. Infant death and mode of birth were most frequently missing. Countries took from under a day to several weeks to set up the CDM, after which the protocol was easy and quick to use.
Conclusion:
This open-source protocol enables rapid production and analysis of perinatal indicators and constitutes a roadmap for a sustainable European information system. It also provides minimum standards for improving national data systems and can be used in other countries to facilitate comparison of perinatal indicators.
Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without ...hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors (D2R). The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation. With the use of the reverse transcriptase PCR technique, D2R mRNA was expressed in all adenomas with very heterogeneous quantity. The expression was very low in corticotroph adenomas (relative median quantity after normalization to housekeeping gene 0.01) and lower in plurihormonal tumors (median 0.4) than in gonadotroph (median 1.3) and null-cell adenomas (median 1.9). The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins. We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity.
Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, ...thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA.
Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene.
The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA.
We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment.
Currently, the public security sector is faced with an increasing administrative burden that limits the ability of police officers to focus on core security tasks. This paper focuses on the ...possibility of using large-scale language models (LSMs) as an innovative tool to address this challenge. Based on a careful literature review and analysis of current trends in artificial intelligence, the author team develops a concept for integrating GPTs into police practice, with an emphasis on the potential for reducing administrative burden and supporting efficient processing of relevant information.
As part of this research, we have identified key areas of policing where AI could bring significant value, including data analysis and document production assistance. However, it should be emphasized that this technology is still in its early stages of development and its implementation would require a carefully considered approach involving interdisciplinary collaboration and further research to test the theoretical assumptions presented in this study.
Thus, this paper contributes to a deeper understanding of the potential benefits and challenges of integrating GPT into policing practice and outlines a path towards future innovative solutions in the field of public safety.
Summary An estimated 2·6 million third trimester stillbirths occurred in 2015 (uncertainty range 2·4–3·0 million). The number of stillbirths has reduced more slowly than has maternal mortality or ...mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals. The Every Newborn Action Plan has the target of 12 or fewer stillbirths per 1000 births in every country by 2030. 94 mainly high-income countries and upper middle-income countries have already met this target, although with noticeable disparities. At least 56 countries, particularly in Africa and in areas affected by conflict, will have to more than double present progress to reach this target. Most (98%) stillbirths are in low-income and middle-income countries. Improved care at birth is essential to prevent 1·3 million (uncertainty range 1·2–1·6 million) intrapartum stillbirths, end preventable maternal and neonatal deaths, and improve child development. Estimates for stillbirth causation are impeded by various classification systems, but for 18 countries with reliable data, congenital abnormalities account for a median of only 7·4% of stillbirths. Many disorders associated with stillbirths are potentially modifiable and often coexist, such as maternal infections (population attributable fraction: malaria 8·0% and syphilis 7·7%), non-communicable diseases, nutrition and lifestyle factors (each about 10%), and maternal age older than 35 years (6·7%). Prolonged pregnancies contribute to 14·0% of stillbirths. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour, or both. Two-thirds of newborns have their births registered. However, less than 5% of neonatal deaths and even fewer stillbirths have death registration. Records and registrations of all births, stillbirths, neonatal, and maternal deaths in a health facility would substantially increase data availability. Improved data alone will not save lives but provide a way to target interventions to reach more than 7000 women every day worldwide who experience the reality of stillbirth.
Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine ...tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, βTSH). Sox2
+
cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2
+
cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2
+
and Sox2
−
groups with respect to the age, initial levels of GH, IGF1, prolactin, βTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2
+
cell count and βTSH immunoreactive cells (
r
= 0.459,
p
< 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2
+
cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2
+
cells are thus commonly present in growth hormone–producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.
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