Critical Duration Index: Anticipating Project Delays From Deterministic Schedule Information

[EN] Classical scheduling techniques are well-known to underestimate the average project duration, yet they remain widely used in practice due to their simplicity. In this paper, the new Critical Duration Index (CDI) is proposed. This index indirectly allows anticipation for the probability of a project ending late, as well as the average project duration extension compared with a deterministic project duration estimate. The accuracy of two simple regression expressions that use the CDI was tested on two representative data sets of 4,100 artificial and 108 empirical (real) projects. Results show that these regression expressions outperformed the only alternative index found in the literature. Besides allowing enhanced forecasting possibilities, calculating the CDI only requires basic scheduling information that is available at the planning stage. It can thus be easily adopted by project managers to improve their project duration estimates over prior deterministic techniques.This research is supported by the National Social Science Fund projects (No. 20BJY010); National Social Science Fund Post-Financing Projects (No. 19FJYB017); Sichuan-Tibet Railway Major Fundamental Science Problems Special Fund (No. 71942006); Qinghai Natural Science Foundation (No. 2020-JY-736); List of Key Science and Technology Projects in China's Transportation Industry in 2018-International Science and Technology Cooperation Project (Nos. 2018-GH-006 and 2019-MS5-100); Emerging Engineering Education Research and Practice Project of Ministry of Education of China (No. E-GKRWJC20202914); Shaanxi Province Higher Education Teaching Reform Project (No. 19BZ016); and Humanities and Social Sciences Research Project of the Ministry of Education (21XJA752003).González-Cruz, M.; Ballesteros-Pérez, P.; Lucko, G.; Zhang, J. (2022). Critical Duration Index: Anticipating Project Delays From Deterministic Schedule Information. Journal of Construction Engineering and Management. 148(11):1-12. https://doi.org/10.1061/(ASCE)CO.1943-7862.00023871121481

Intracerebroventricular administration of the thyroid hormone analog TRIAC increases its brain content in the absence of MCT8

Patients lacking the thyroid hormone (TH) transporter MCT8 present abnormal serum levels of TH: low thyroxine and high triiodothyronine. They also have severe neurodevelopmental defects resulting from cerebral hypothyroidism, most likely due to impaired TH transport across the brain barriers. The use of TH analogs, such as triiodothyroacetic acid (TRIAC), that can potentially access the brain in the absence of MCT8 and restore at least a subset of cerebral TH actions could improve the neurological defects in these patients. We hypothesized that direct administration of TRIAC into the brain by intracerebroventricular delivery to mice lacking MCT8 could bypass the restriction at the brain barriers and mediate TH action without causing hypermetabolism. We found that intracerebroventricular administration of therapeutic doses of TRIAC does not increase further plasma triiodothyronine or further decrease plasma thyroxine levels and does not alter TH content in the cerebral cortex. Although TRIAC content increased in the brain, it did not induce TH-mediated actions on selected target genes. Our data suggest that intracerebroventricular delivery of TRIAC has the ability to target the brain in the absence of MCT8 and should be further investigated to address its potential therapeutic use in MCT8 deficiency.This work was funded by the Spanish Plan Nacional de I+D+i (grant number SAF2017-86342-R to AG-F), the Sherman Foundation (OTR02211 to AG-F and SB-L), the Center for Biomedical Research on Rare Diseases (Ciberer to AG-F and CG-M), Instituto de Salud Carlos III, Madrid, Spain. X-HL and SR were supported in part by grant DK 15070 from the National Institutes of Health, USA

Contrasting P-T-t-d paths of the polycyclic Palaeozoic tectono-metamorphic event in the Southern Chinese Altai: an example from Kalasu area

To understand the polycyclic Palaeozoic tectono-metamorphic evolution of the Southern Chinese Altai, petrological and structural studies together with thermodynamic modelling and dating were carried out in the Cambro-Ordovician metapelitic sequence of the Kalasu area. The sequence is divided into upper, middle and lower crustal orogenic levels according to their metamorphic grade and structural patterns. Metamorphism increases from low to high-grade towards the deeper crustal levels with garnet-biotite schists in the upper crustal level, sillimanite-garnet and staurolite-garnet-sillimanite schists and gneisses in the middle crustal level, and cordierite-sillimanite-K-feldspar migmatites in the lower crustal level. Structural succession involves a subhorizontal S1 foliation folded by NE-SW open to tight and upright F2 folds (with no metamorphism associated), reworking by an orthogonal D3 deformation, characterized by NW-SE open to close F3 folds with moderately plunging axes, steeply dipping S3 axial planes and S3 cleavage. Early Devonian calc-alkaline granitoids intruded the sequence parallel to S1 foliation, whereas Permian undeformed gabbroic bodies were emplaced in the lower crust and granites in the upper crust coevally with D3. The P-T-t-d paths indicate that the crystalline rocks underwent a clockwise evolution marked by Early Devonian burial associated with heating, followed by Permian decompression, in agreement with studies from other parts of the Chinese Altai. The burial is recorded in the middle and lower levels by the presence of g-st-ky-ru relics within the S1 fabric. This stage is related to crustal thickening, whereas heating is related to intrusions of Devonian granite sheets during an extensional setting. A subsequent decompression (around 3-5 kbar) is recorded in all crustal levels, associated with intrusions of gabbro and granite along the southern border of the Chinese Altai and coeval with the last Permian deformation. This last stage is related to the collision between the Junggar arc system and the Chinese Altai orogenic belt

Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes

In normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)–mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study has characterized the role of PDK1 in the pathology caused by deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN). PDK1 is shown to be essential for lymphomagenesis caused by deletion of PTEN in T cell progenitors. However, PTEN deletion bypasses the normal PDK1-controlled signaling pathways that determine thymocyte growth and proliferation. PDK1 does have important functions in PTEN-null thymocytes, notably to control the PKB–Foxo signaling axis and to direct the repertoire of adhesion and chemokine receptors expressed by PTEN-null T cells. The results thus provide two novel insights concerning pathological signaling caused by PTEN loss in lymphocytes. First, PTEN deletion bypasses the normal PDK1-controlled metabolic checkpoints that determine cell growth and proliferation. Second, PDK1 determines the cohort of chemokine and adhesion receptors expressed by PTEN-null cells, thereby controlling their migratory capacity

DMRT1 regulates human germline commitment

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis

Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN)

Background. In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function. Methods. An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least three pathologists with an average final score reported. Results. We assessed 35 males (mean age 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The average serum creatinine was 1.3mg/dl (114.9 μmol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m2 and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had significantly more proximal tubule, peritubular capillary and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had significantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Significant changes, including segmental and global sclerosis, and interstitial fibrosis were seen even in patients with stage 1-2 chronic kidney disease with minimal proteinuria. Conclusions. The development of a standardized scoring system of both disease-specific lesions, i.e. lipid deposition related, and general lesions of progression, i.e. fibrosis and sclerosis, showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These findings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for longitudinal assessment of prognosis and responses to therapy for Fabry nephropath

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

A tale of worldwide success: Behind the scenes of Carex (Cyperaceae) biogeography and diversification

The megadiverse genus Carex (c. 2000 species, Cyperaceae) has a nearly cosmopolitan distribution, displaying an inverted latitudinal richness gradient with higher species diversity in cold-temperate areas of the Northern Hemisphere. Despite great expansion in our knowledge of the phylogenetic history of the genus and many molecular studies focusing on the biogeography of particular groups during the last few decades, a global analysis of Carex biogeography and diversification is still lacking. For this purpose, we built the hitherto most comprehensive Carex-dated phylogeny based on three markers (ETS–ITS–matK), using a previous phylogenomic Hyb-Seq framework, and a sampling of two-thirds of its species and all recognized sections. Ancestral area reconstruction, biogeographic stochastic mapping, and diversification rate analyses were conducted to elucidate macroevolutionary biogeographic and diversification patterns. Our results reveal that Carex originated in the late Eocene in E Asia, where it probably remained until the synchronous diversification of its main subgeneric lineages during the late Oligocene. E Asia is supported as the cradle of Carex diversification, as well as a “museum” of extant species diversity. Subsequent “out-of-Asia” colonization patterns feature multiple asymmetric dispersals clustered toward present times among the Northern Hemisphere regions, with major regions acting both as source and sink (especially Asia and North America), as well as several independent colonization events of the Southern Hemisphere. We detected 13 notable diversification rate shifts during the last 10 My, including remarkable radiations in North America and New Zealand, which occurred concurrently with the late Neogene global cooling, which suggests that diversification involved the colonization of new areas and expansion into novel areas of niche space.This work was carried out with financial support by the National Science Foundation (Award #1255901 to ALH and Award #1256033 to EHR), the Spanish Ministry of Economy and Competitiveness (project CGL2016–77401‐P to SM-B and ML), the USDA National Institute of Food and Agriculture (McIntire Stennis project 1018692 to DS) as well as postdoctoral fellowships towards SM‐B (Universidad Pablo de Olavide, PP16/12‐APP), and PJ‐M (National Science Foundation, Award #1256033, and the Smithsonian Postdoctoral Fellowship program)