Explore the vast range of titles available.

Reciprocal feedback processes between experience and development are central to contemporary developmental theory. Autoregressive cross-lagged panel (ARCL) models represent a common analytic approach intended to test such dynamics. The authors demonstrate that—despite the ARCL model's intuitive appeal—it typically (a) fails to align with the theoretical processes that it is intended to test and (b) yields estimates that are difficult to interpret meaningfully. Specifically, using a Monte Carlo simulation and two empirical examples concerning the reciprocal relation between spanking and child aggression, it is shown that the cross-lagged estimates derived from the ARCL model reflect a weighted—and typically uninterpretable—amalgam of between- and within-person associations. The authors highlight one readily implemented respecification that better addresses these multiple levels of inference.

ContextA hairy requirements engineering (RE) task involving natural language (NL) documents is (1) a non-algorithmic task to find all relevant answers in a set of documents, that is (2) not inherently difficult for NL-understanding humans on a small scale, but is (3) unmanageable in the large scale. In performing a hairy RE task, humans need more help finding all the relevant answers than they do in recognizing that an answer is irrelevant. Therefore, a hairy RE task demands the assistance of a tool that focuses more on achieving high recall, i.e., finding all relevant answers, than on achieving high precision, i.e., finding only relevant answers. As close to 100% recall as possible is needed, particularly when the task is applied to the development of a high-dependability system. In this case, a hairy-RE-task tool that falls short of close to 100% recall may even be useless, because to find the missing information, a human has to do the entire task manually anyway. On the other hand, too much imprecision, too many irrelevant answers in the tool’s output, means that manually vetting the tool’s output to eliminate the irrelevant answers may be too burdensome. The reality is that all that can be realistically expected and validated is that the recall of a hairy-RE-task tool is higher than the recall of a human doing the task manually.ObjectiveTherefore, the evaluation of any hairy-RE-task tool must consider the context in which the tool is used, and it must compare the performance of a human applying the tool to do the task with the performance of a human doing the task entirely manually, in the same context. The context of a hairy-RE-task tool includes characteristics of the documents being subjected to the task and the purposes of subjecting the documents to the task. However, traditionally, many a hairy-RE-task tool has been evaluated by considering only (1) how high is its precision, or (2) how high is its F-measure, which weights recall and precision equally, ignoring the context, and possibly leading to incorrect — often underestimated — conclusions about how effective it is.MethodTo evaluate a hairy-RE-task tool, this article offers an empirical procedure that takes into account not only (1) the performance of the tool, but also (2) the context in which the task is being done, (3) the performance of humans doing the task manually, and (4) the performance of those vetting the tool’s output. The empirical procedure uses (I) on one hand, (1) the recall and precision of the tool, (2) a contextually weighted F-measure for the tool, (3) a new measure called summarization of the tool, and (4) the time required for vetting the tool’s output, and (II) on the other hand, (1) the recall and precision achievable by and (2) the time required by a human doing the task.ResultsThe use of the procedure is shown for a variety of different contexts, including that of successive attempts to improve the recall of an imagined hairy-RE-task tool. The procedure is shown to be context dependent, in that the actual next step of the procedure followed in any context depends on the values that have emerged in previous steps.ConclusionAny recommendation for a hairy-RE-task tool to achieve close to 100% recall comes with caveats and may be required only in specific high-dependability contexts. Appendix C applies parts of this procedure to several hairy-RE-task tools reported in the literature using data published about them. The surprising finding is that some of the previously evaluated tools are actually better than they were thought to be when they were evaluated using mainly precision or an unweighted F-measure.

Cold temperatures induce formation of beige adipocytes, which convert glucose and fatty acids to heat, and may increase energy expenditure, reduce adiposity and lower blood glucose. This therapeutic potential is unrealized, hindered by a dearth of genetic tools to fate map, track and manipulate beige progenitors and ‘beiging’. Here we examined 12 Cre/inducible Cre mouse strains that mark adipocyte, muscle and mural lineages, three proposed beige origins. Among these mouse strains, only those that marked perivascular mural cells tracked the cold-induced beige lineage. Two SMA-based strains, SMA-Cre ERT2 and SMA-rtTA, fate mapped into the majority of cold-induced beige adipocytes and SMA-marked progenitors appeared essential for beiging. Disruption of the potential of the SMA-tracked progenitors to form beige adipocytes was accompanied by an inability to maintain body temperature and by hyperglycaemia. Thus, SMA-engineered mice may be useful to track and manipulate beige progenitors, beige adipocyte formation and function. Beige adipocytes are formed in response to cold and thought to contribute to organismal energy homeostasis. Here, the authors study a range of conditional and inducible RFP-expressing Cre mouse strains and find that SMA-based lines are the most useful for mapping beige adipocyte progenitor cells.

Background Revision THA and TKA are growing and important clinical and economic challenges. Healthcare systems tend to combine revision joint replacement procedures into a single service line, and differences between revision THA and revision TKA remain incompletely characterized. These differences carry implications for guiding care and resource allocation. We therefore evaluated epidemiologic trends associated with revision THAs and TKAs. Questions/purposes We sought to determine differences in (1) the number of patients undergoing revision TKA and THA and respective demographic trends; (2) differences in the indications for and types of revision TKA and THA; (3) differences in patient severity of illness scoring between THA and TKA; and (4) differences in resource utilization (including cost and length of stay [LOS]) between revision THA and TKA. Methods The Nationwide Inpatient Sample (NIS) was used to evaluate 235,857 revision THAs and 301,718 revision TKAs between October 1, 2005 and December 31, 2010. Patient characteristics, procedure information, and resource utilization were compared across revision THAs and TKAs. A revision burden (ratio of number of revisions to total number of revision and primary surgeries) was calculated for hip and knee procedures. Severity of illness scoring and cost calculations were derived from the NIS. As our study was principally descriptive, statistical analyses generally were not performed; however, owing to the large sample size available to us through this NIS analysis, even small observed differences presented are likely to be highly statistically significant. Results Revision TKAs increased by 39% (revision burden, 9.1%–9.6%) and THAs increased by 23% (revision burden, 15.4%–14.6%). Revision THAs were performed more often in older patients compared with revision TKAs. Periprosthetic joint infection (25%) and mechanical loosening (19%) were the most common reasons for revision TKA compared with dislocation (22%) and mechanical loosening (20%) for revision THA. Full (all-component) revision was more common in revision THAs (43%) than in TKAs (37%). Patients who underwent revision THA generally were sicker (> 50% major severity of illness score) than patients who underwent revision TKA (65% moderate severity of illness score). Mean LOS was longer for revision THAs than for TKAs. Mean hospitalization costs were slightly higher for revision THA (USD 24,697 +/− USD 40,489 [SD]) than revision TKA (USD 23,130 +/− USD 36,643 [SD]). Periprosthetic joint infection and periprosthetic fracture were associated with the greatest LOS and costs for revision THAs and TKAs. Conclusions These data could prove important for healthcare systems to appropriately allocate resources to hip and knee procedures: the revision burden for THA is 52% greater than for TKA, but revision TKAs are increasing at a faster rate. Likewise, the treating clinician should understand that while both revision THAs and TKAs bear significant clinical and economic costs, patients undergoing revision THA tend to be older, sicker, and have greater costs of care.

Beige/brite adipocytes are induced within white adipose tissues (WAT) and, when activated, consume glucose and fatty acids to produce heat. Classically, two stimuli have been used to trigger a beiging response: cold temperatures and β3-adrenergic receptor (Adrb3) agonists. These two beiging triggers have been used interchangeably but whether these two stimuli may induce beiging differently at cellular and molecular levels remains unclear. Here, we found that cold-induced beige adipocyte formation requires Adrb1, not Adrb3, activation. Adrb1 activation stimulates WAT resident perivascular (Acta2+) cells to form cold-induced beige adipocytes. In contrast, Adrb3 activation stimulates mature white adipocytes to convert into beige adipocytes. Necessity tests, using mature adipocyte-specific Prdm16 deletion strategies, demonstrated that adipocytes are required and are predominant source to generate Adrb3-induced, but not cold-induced, beige adipocytes. Collectively, we identify that cold temperatures and Adrb3 agonists activate distinct cellular populations that express different β-adrenergic receptors to induce beige adipogenesis. Excess accumulation of a type of fat called white fat is associated with obesity and metabolic problems. White fat cells store energy. White fat tissue also contains some beige fat cells, which burn fats and sugars to produce heat. Cold temperatures trigger the production and activity of beige fat cells, which allows the body to stay warm. People with obesity tend to have less beige fat and more white fat. This has led scientists to test whether treatments that increase the number of beige fat cells a person has could reduce fat mass and improve metabolism. To develop treatments that increase beige fat, scientists must first understand where it comes from and how cold and other factors stimulate its growth. Recent studies have shown that smooth muscle cells, which surround blood vessel walls, make cold-induced beige fat cells. A widely used drug that turns on the β3 adrenergic receptor, which is found in the cell membrane, also boosts the creation of beige fat cells. Yet, it was not clear exactly how cold or this drug triggers the production of beige fat. Now, Jiang et al. show that drugs that target β3 adrenergic receptors cause white fat cells in mice to change into beige fat cells. The experiments also showed that cold turns on a different receptor called the β1 adrenergic receptor on smooth muscle cells causing them to make beige fat cells. This shows that there is more than one source for beige fat cells in the body and that different strategies for increasing beige fat cell numbers do not work the same way. More studies are needed to learn whether beige fat cells produced after exposure to cold or drugs behave in the same way and have similar affects on metabolism. This could help scientists determine if one of these strategies could make a better treatment for obesity or other metabolic disorders.

Background The impact of specific baseline comorbid conditions on the relative risk of postoperative mortality and periprosthetic joint infection (PJI) in elderly patients undergoing TKA has not been well defined. Questions/purposes We calculated the relative risk of postoperative mortality and PJI associated with 29 comorbid conditions in Medicare patients undergoing TKA. Patients and Methods The Medicare 5% sample was used to calculate the relative risk of 90-day postoperative mortality and PJI as a function of 29 preexisting comorbid conditions in 83,011 patients who underwent primary TKA between 1998 and 2007. Results The independent risk factors for 90-day postoperative mortality (in decreasing order of significance) were congestive heart failure, metastatic cancer, renal disease, peripheral vascular disease, cerebrovascular disease, lymphoma, cardiac arrhythmia, dementia, pulmonary circulation disorders, and chronic liver disease. The independent risk factors for PJI (in decreasing order of significance) were congestive heart failure, chronic pulmonary disease, preoperative anemia, diabetes, depression, renal disease, pulmonary circulation disorders, obesity, rheumatologic disease, psychoses, metastatic tumor, peripheral vascular disease, and valvular disease. Conclusions We believe this information important when counseling elderly patients regarding the risks of mortality and PJI after TKA and risk-adjusting publicly reported TKA patient outcomes. Level of Evidence Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Perivascular adipocyte progenitor cells (APCs) can generate cold temperature-induced thermogenic beige adipocytes within white adipose tissue (WAT), an effect that could counteract excess fat mass and metabolic pathologies. Yet, the ability to generate beige adipocytes declines with age, creating a key challenge for their therapeutic potential. Here we show that ageing beige APCs overexpress platelet derived growth factor receptor beta ( Pdgfrβ ) to prevent beige adipogenesis. We show that genetically deleting Pdgfrβ , in adult male mice, restores beige adipocyte generation whereas activating Pdgfrβ in juvenile mice blocks beige fat formation. Mechanistically, we find that Stat1 phosphorylation mediates Pdgfrβ beige APC signaling to suppress IL-33 induction, which dampens immunological genes such as IL-13 and IL-5 . Moreover, pharmacologically targeting Pdgfrβ signaling restores beige adipocyte development by rejuvenating the immunological niche. Thus, targeting Pdgfrβ signaling could be a strategy to restore WAT immune cell function to stimulate beige fat in adult mammals. Thermogenic beige fat can reduce fat mass and improve metabolic health, yet the ability to form beige fat rapidly declines with age. Here, the authors show that targeting the age-related ramping of Pdgfrβ signalling restores the ageing adipose tissue niche to ignite beige fat development.

Understanding the cause of failure and type of revision total knee arthroplasty (TKA) procedures performed in the United States is essential in guiding research, implant design, and clinical decision making in TKA. We assessed the causes of failure and specific types of revision TKA procedures performed in the United States using newly implemented ICD-9-CM diagnosis and procedure codes related to revision TKA data from the Nationwide Inpatient Sample (NIS) database. Clinical, demographic, and economic data were reviewed and analyzed from 60,355 revision TKA procedures performed in the United States between October 1, 2005 and December 31, 2006. The most common causes of revision TKA were infection (25.2%) and implant loosening (16.1%), and the most common type of revision TKA procedure reported was all component revision (35.2%). Revision TKA procedures were most commonly performed in large, urban, nonteaching hospitals in Medicare patients ages 65 to 74. The average length of hospital stay (LOS) for all revision TKA procedures was 5.1 days, and the average total charges were $49,360. However, average LOS, average charges, and procedure frequencies varied considerably by census region, hospital type, and procedure performed. Level of Evidence: Level II, economic and decision analysis. See Guidelines for Authors for a complete description of levels of evidence.

Sex steroids modulate the distribution of mammalian white adipose tissues. Moreover, WAT remodeling requires adipocyte progenitor cells. Nevertheless, the sex-dependent mechanisms regulating adipocyte progenitors remain undetermined. Here, we uncover Cxcr4 acting in a sexually dimorphic manner to affect a pool of proliferating cells leading to restriction of female fat mass. We find that deletion of Cxcr4 in Pparγ -expressing cells results in female, not male, lipodystrophy, which cannot be restored by high-fat diet consumption. Additionally, Cxcr4 deletion is associated with a loss of a pool of proliferating adipocyte progenitors. Cxcr4 loss is accompanied by the upregulation of estrogen receptor alpha in adipose-derived PPARγ-labelled cells related to estradiol hypersensitivity and stalled adipogenesis. Estrogen removal or administration of antiestrogens restores WAT accumulation and dynamics of adipose-derived cells in Cxcr4 -deficient mice. These findings implicate Cxcr4 as a female adipogenic rheostat, which may inform strategies to target female adiposity. Sex steroid receptor activity controls the distribution and growth of adipose tissues. Here, the authors reveal that Cxcr4 regulates the Pparg-marked adipose lineage to restrict female fat mass by modifying estrogen receptor expression and activity.

It currently is believed that vitamin A, retinol, functions through active metabolites: the visual chromophore 11-cis-retinal, and retinoic acids, which regulate gene transcription. Retinol circulates in blood bound to retinol-binding protein (RBP) and is transported into cells by a membrane protein termed \"stimulated by retinoic acid 6\" (STRA6). We show here that STRA6 not only is a vitamin A transporter but also is a cell-surface signaling receptor activated by the RBP-retinol complex. Association of RBP-retinol with STRA6 triggers tyrosine phosphorylation, resulting in recruitment and activation of JAK2 and the transcription factor STAT5. The RBP-retinol/STRA6/JAK2/STAT5 signaling cascade induces the expression of STAT target genes, including suppressor of cytokine signaling 3 (SOCS3), which inhibits insulin signaling, and peroxisome proliferator-activated receptor gamma (PPARγ), which enhances lipid accumulation. These observations establish that the parental vitamin A molecule is a transcriptional regulator in its own right, reveal that the scope of biological functions of the vitamin is broader than previously suspected, and provide a rationale for understanding how RBP and retinol regulate energy homeostasis and insulin responses.