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The economic production of gas and oil from shales requires repeated hydraulic fracturing operations to stimulate these tight reservoir rocks. Besides simple depletion, the often observed decay of production rate with time may arise from creep-induced fracture closure. We examined experimentally the creep behavior of an immature carbonate-rich Posidonia shale, subjected to constant stress conditions at temperatures between 50 and 200 °C and confining pressures of 50–200 MPa, simulating elevated in situ depth conditions. Samples showed transient creep in the semibrittle regime with high deformation rates at high differential stress, high temperature and low confinement. Strain was mainly accommodated by deformation of the weak organic matter and phyllosilicates and by pore space reduction. The primary decelerating creep phase observed at relatively low stress can be described by an empirical power law relation between strain and time, where the fitted parameters vary with temperature, pressure and stress. Our results suggest that healing of hydraulic fractures at low stresses by creep-induced proppant embedment is unlikely within a creep period of several years. At higher differential stress, as may be expected in situ at contact areas due to stress concentrations, the shale showed secondary creep, followed by tertiary creep until failure. In this regime, microcrack propagation and coalescence may be assisted by stress corrosion. Secondary creep rates were also described by a power law, predicting faster fracture closure rates than for primary creep, likely contributing to production rate decline. Comparison of our data with published primary creep data on other shales suggests that the long-term creep behavior of shales can be correlated with their brittleness estimated from composition. Low creep strain is supported by a high fraction of strong minerals that can build up a load-bearing framework.

Background Barth syndrome (BTHS) is a rare, X-linked disorder that stems from mutations in the TAFAZZIN (TAZ) gene with varying disease severity among patients. The Barth Syndrome Symptom Assessment (BTHS-SA) is a patient-reported outcome questionnaire developed to assess BTHS symptom severity. The current study reflects the first exploration of the assessment’s psychometric performance. Methods The BTHS-SA was administered in TAZPOWER, a phase 2, randomized, double-blind, placebo-controlled crossover study to evaluate daily subcutaneous injections of elamipretide in subjects with genetically confirmed BTHS. Descriptive and correlational analyses were used to assess the score distributions, reliability, and construct-related validity of BTHS-SA items and domains including a two-item (2 FS), three-item (3 FS), and four-item (4 FS) fatigue score, and a five-item myopathy score (5MS). Results Among the N = 12 white males (M age = 19.5, SD = 7.7) participating in the TAZPOWER trial, overall symptoms were rated as mild (n = 5, 41.7%), moderate (n = 5, 41.7%), severe (n = 1, 8.3%), or very severe (n = 1, 8.3%). Descriptive statistics for the BTHS-SA scores indicate variability of symptom severity both within symptom cluster and across patients. Promising results were found for both internal consistency (α = 0.67, 0.72, and 0.66 for the 3 FS, 4 FS, and 5MS, respectively) and test–retest reliability (ICC values ranging from 0.79 to 0.94 across two test–retest intervals). Correlational analyses showing moderate to strong relationships to other patient reports of fatigue (e.g., r = 0.59, 0.76, 0.68, and 0.61 between the PROMIS Fatigue SF and the 2 FS, 3 FS, 4 FS, and 5MS, respectively) and symptom severity (e.g., r = 0.60, 0.62, 0.56, 0.53 between a patient global rating and the 2 FS, 3 FS, 4 FS, and 5MS, respectively) support the measure’s convergent validity. A similar pattern of relationships was observed when correlating changes in BTHS-SA scores to reference measures, including moderate to strong relationships between the BTHS-SA and direct patient reports of change (r = 0.81, 0.79, 0.82, and 0.80 between a global impression of change score and the 2 FS, 3 FS, 4 FS, and 5MS, respectively). Conclusion Though the small sample size limits strong conclusions, this analysis suggests the BTHS-SA can produce reliable scores upon which valid inferences may be drawn. The BTHS-SA may be a useful tool to evaluate treatment benefits in this underserved population. Trial registration ClinicalTrials.gov identifier, NCT03098797. Registered 05 May 2017, https://www.clinicaltrials.gov/study/NCT03098797 .

The transition into school occurs at the intersection of multiple environmental settings. This study applied growth curve modeling to a sample of 1,364 American children, followed from birth through age 6, who had been categorized by their exposure to cognitive stimulation at home and in preschool child care and lst-grade classrooms. Of special interest was the unique and combined contribution to early learning of these 3 settings. Net of socioeconomic selection into different settings, children had higher math achievement when they were consistently stimulated in all 3, and they had higher reading achievement when consistently stimulated at home and in child care. The observed benefits of consistent environmental stimulation tended to be more pronounced for low-income children.

The calcium carbonate shells of planktic foraminifera provide our most valuable geochemical archive of ocean surface conditions and climate spanning the last 100 million years, and play an important role in the ocean carbon cycle. These shells are preserved in marine sediments as calcite, the stable polymorph of calcium carbonate. Here, we show that shells of living planktic foraminifers Orbulina universa and Neogloboquadrina dutertrei originally form from the unstable calcium carbonate polymorph vaterite, implying a non-classical crystallisation pathway involving metastable phases that transform ultimately to calcite. The current understanding of how planktic foraminifer shells record climate, and how they will fare in a future high-CO 2 world is underpinned by analogy to the precipitation and dissolution of inorganic calcite. Our findings require a re-evaluation of this paradigm to consider the formation and transformation of metastable phases, which could exert an influence on the geochemistry and solubility of the biomineral calcite. Understanding foraminifera mineralisation pathways is essential to correctly decipher the geochemical climate signals recorded in their shells. Here, the authors identify a non-classical crystallization pathway via metastable phases for Orbulina universa and Neogloboquadrina dutertrei .

Background Scale development is a complex activity requiring significant investments of time and money to produce evidence of a scale’s ability to produce reliable scores and valid inferences. With increasing use of clinical outcome assessments (COAs) in medical product development, evidentiary expectations of regulatory bodies to support inferences are a key consideration. The goal of this paper is to demonstrate how existing methods in measurement science can be used to identify and fill evidence gaps when considering re-purposing an existing scale for a new use case (e.g., new patient population, altering the recall period), rather than creating a new COA tool. Methods We briefly review select validity theory and psychometric concepts, linking them to the nomenclature in the COA/regulated space. Four examples (two in-text and two in online supplemental materials) of modifications are presented to demonstrate these ideas in practice for quality of life (QOL)-related measures. Results Each example highlights the initial process of evaluating the desired validity claims, identifying gaps in evidence to support these claims, and determining how such gaps could be filled, often without having to develop a new measure. Conclusions If an existing scale, with minimal modification or additional evidence, can be shown to be fit for a new purpose, considerable effort can be saved and research waste avoided. In many cases, a new instrument is simply unnecessary. Far better to recycle an “old” scale for a new use–with sufficient evidence that it is fit for that purpose–than to “buy” a new one.

Objective:Homozygous deletions/mutations of the SMN1 gene cause infantile spinal muscular atrophy (SMA). The presence of at least one SMN2 gene copy is required for normal embryogenesis. Lack of SMN protein results in degeneration of motor neurons, while extraneuronal manifestations have been regarded as a chance association with SMA. We report on heart defects in the subgroup of congenital SMA type I patients.Methods:Data were recruited from 65 unselected SMA I patients whose diagnosis had been confirmed genetically within the first 6 months of age. SMN2 copy numbers were analysed retrospectively and correlated with clinical findings including heart malformations.Results:Four (6%) patients had one copy of SMN2, 56 (86%) had two and five (8%) had three SMN2 copies. Three out of four (75%) patients with a single SMN2 copy had congenital SMA with haemodynamically relevant atrial or ventricular septal defects.Conclusions:Previous case reports of SMA I patients with congenital heart defects did not clarify whether the cardiac malformations were coincidental. Given the respective incidences of congenitally lethal SMA with a single SMN2 copy and of cardiac septal defects in humans, a chance association of both conditions would occur in less than one out of 50 million individuals. Our findings suggest that the SMN protein is relevant for normal cardiogenesis.

Purpose We examined the reliability and validity of the 6-item Headache Impact Test (HIT-6) specifically on patients with chronic migraine (CM) from the PROMISE-2 clinical trial. Methods The conceptual framework of HIT-6 was evaluated using baseline data from the PROMISE-2 study (NCT02974153; N  = 1072). A unidimensional graded response model within the item response theory (IRT) framework was used to evaluate model fit and item characteristics. Using baseline and week 12 data, convergent and discriminant validity of the HIT-6 was evaluated by correlation coefficients. Sensitivity to change was assessed by evaluating correlations between HIT-6 scores and change scores for other established reference measures. All examined correlations were specified a priori with respect to direction and magnitude. Known-groups analyses were anchored using Patient Global Impression of Change and monthly headache days at week 12. Results A unidimensional model fit the data well, supporting that the 6 items measure a single construct. All item slopes and thresholds were within acceptable ranges. In both the validity and sensitivity to change analyses, all observed correlations conformed to directional expectations, and most conformed to magnitude expectations. Known-groups analyses demonstrated that the HIT-6 total score can distinguish between clinically meaningful CM subgroups. Conclusion The HIT-6 was successfully calibrated using IRT with data from PROMISE-2. Results from these analyses were generally consistent with previous literature and provided supportive evidence that the HIT-6 is well suited for measuring the impact of headache and migraine in the CM population.

Metamorphic diamonds hosted by major and accessory phases in ultrahigh-pressure (UHP) metamorphic terranes represent important indicators of deep subduction and exhumation of continental crust at convergent plate boundaries. However, their nucleation and growth mechanisms are not well understood due to their small size and diversity. The Bohemian microdiamond samples represent a unique occurrence of monocrystalline octahedral and polycrystalline cubo-octahedral microdiamonds in two different metasedimentary rock types. By combining new and published data on microdiamonds (morphology, resorption, associated phases, carbon isotope composition) with P–T constraints from their host rocks, we demonstrate that the peak P–T conditions for the diamond-bearing UHP rocks cluster along water activity-related phase transitions that determine the microdiamond features. With increasing temperature, the diamond-forming medium changes from aqueous fluid to hydrous melt, and diamond morphology evolves from cubo-octahedral to octahedral. The latter is restricted to the UHP-UHT rocks exceeding 1100 °C, which is above the incongruent melting of phengite, where microdiamonds nucleate along a prograde P–T path in silicate-carbonate hydrous melt. The observed effect of temperature on diamond morphology supports experimental data on diamond growth and can be used for examining growth conditions of cratonic diamonds from kimberlites, which are dominated by octahedra and their resorbed forms.

Megacrystic sapphires are frequently associated with alkaline basalts, most notably in Asia and Australia, although basalt is not generally normative in corundum. Most of these sapphire occurrences are located in alluvial or eluvial deposits, making it difficult to study the enigmatic relationship between the sapphires and their host rocks. Here, we present detailed petrological and geochemical investigations of in situ megacrystic sapphires within alkaline basalts from the Cenozoic Siebengebirge Volcanic Field (SVF) in Germany. Markedly, the sapphires show several micrometer thick spinel coronas at the contact with the host basalt, indicating chemical disequilibrium between the sapphire and the basaltic melt, supporting a xenogenetic relationship. However, in situ U–Pb dating of a Columbite Group inclusion within one Siebengebirge sapphire using laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) indicates a close genetic relationship between sapphire crystallization and alkaline mafic volcanism in the SVF. The syngenetic mineral inclusion suite including carbonates, members of the Pyrochlore, Betafite and Columbite Groupe minerals, as well as a high abundance of HFSE and of gaseous low-density CO 2 inclusions support a parentage of a highly evolved, MgO and FeO deficient carbonatitic melt. We identified CO 2 to be the link between alkaline basaltic volcanism and the xenocrystic sapphires. Only alkaline volcanic suites can build up enough CO 2 in this magma chamber upon fractionation so that at high degrees of fractionation a carbonatitic melt exsolves which in turn can crystallize sapphires.

Purpose Measurement invariance issues should be considered during test construction. In this paper, we provide a conceptual overview of measurement invariance and describe how the concept is implemented in several different statistical approaches. Typical applications look for invariance over things such as mode of administration (paper and pencil vs. computer based), language/translation, age, time, and gender, to cite just a few examples. To the extent that the relationships between items and constructs are stable/invariant, we can be more confident in score interpretations. Methods A series of simulated examples are reported which highlight different kinds of non-invariance, the impact it can have, and the effect of appropriately modeling a lack of invariance. One example focuses on the longitudinal context, where measurement invariance is critical to understanding trends over time. Software syntax is provided to help researchers apply these models with their own data. Results The simulation studies demonstrate the negative impact an erroneous assumption of invariance may have on scores and substantive conclusions drawn from naively analyzing those scores. Conclusions Measurement invariance implies that the links between the items and the construct of interest are invariant over some domain, grouping, or classification. Examining a new or existing test for measurement invariance should be part of any test construction/implementation plan. In addition to reviewing implications of the simulation study results, we also provide a discussion of the limitations of current approaches and areas in need of additional research.