The incidence of lower gastrointestinal bleeding (LGIB) is increasing; however, predictors of outcomes for patients with LGIB are not as well defined as those for patients with upper gastrointestinal bleeding (UGIB). The aim of this study was to identify the clinical outcomes and the predictors of poor outcomes for patients with LGIB, compared to outcomes for patients with UGIB. We identified patients with LGIB or UGIB who underwent endoscopic procedures between July 2006 and February 2013. Propensity score matching was used to improve comparability between LGIB and UGIB groups. The clinical outcomes and predictors of 30-day rebleeding and mortality rate were analyzed between the two groups. In total, 601 patients with UGIB (n = 500) or LGIB (n = 101) were included in the study, and 202 patients with UGIB and 101 patients with LGIB were analyzed after 2:1 propensity score matching. The 30-day rebleeding and mortality rates were 9.9% and 4.5% for the UGIB group, and 16.8% and 5.0% for LGIB group, respectively. After logistic regression analysis, the Rockall score (P = 0.013) and C-reactive protein (CRP; P = 0.047) levels were significant predictors of 30-day mortality in patients with LGIB; however, we could not identify any predictors of rebleeding in patients with LGIB. The clinical outcomes for patients with LGIB are not better than clinical outcomes for patients with UGIB. The clinical Rockall score and serum CRP levels may be used to predict 30-day mortality in patients with LGIB.

If company revenues fluctuate, the resulting volatility makes it more difficult to project the company’s future revenues and earnings and ensure steady cash-flow. This lessens investor confidence and, as such, can harm the financial health of a brand. So, effective marketing can have undesired financial side effects.

Although volatile marketing spending, as opposed to even-level spending, may improve a brand’s financial performance, it can also increase the volatility of performance, which is not a desirable outcome. This article analyzes how revenue and cash-flow volatility are influenced by own and competitive marketing spending volatility, by the level of marketing spending, by the responsiveness to own marketing spending, and by competitive response. From market response theory, we derive propositions about the influence of these variables on revenue and cash-flow volatility. In addition, we extend the Dorfman–Steiner theorem to derive the optimal level and volatility of expenditures if volatility effects are taken into account. Based on a large sample of 99 pharmaceutical brands in four clinical categories and four European countries, we test for the empirical relevance of the propositions and assess the magnitude of the different sources of marketing-induced performance volatility. We find broad support for the predicted volatility effects. Volatility elasticities are significant and may be as large as 1.10 for cash-flow variance with respect to marketing responsiveness. The findings imply that common volatility-increasing marketing practices such as price promotions or volatile advertising plans may be effective at the top line, but they could turn out to be ineffective after all costs are taken into account. Optimal marketing volatility needs to trade off sales effectiveness and extra costs resulting from marketing volatility. This paper was accepted by Pradeep K. Chintagunta, marketing.

Although volatile marketing spending, as opposed to even-level spending, may improve a brand’s financial performance, it can also increase the volatility of performance, which is not a desirable outcome. This article analyzes how revenue and cash-flow volatility are influenced by own and competitive marketing spending volatility, by the level of marketing spending, by the responsiveness to own marketing spending, and by competitive response. From market response theory, we derive propositions about the influence of these variables on revenue and cash-flow volatility. In addition, we extend the Dorfman–Steiner theorem to derive the optimal level and volatility of expenditures if volatility effects are taken into account. Based on a large sample of 99 pharmaceutical brands in four clinical categories and four European countries, we test for the empirical relevance of the propositions and assess the magnitude of the different sources of marketing-induced performance volatility. We find broad support for the predicted volatility effects. Volatility elasticities are significant and may be as large as 1.10 for cash-flow variance with respect to marketing responsiveness. The findings imply that common volatility-increasing marketing practices such as price promotions or volatile advertising plans may be effective at the top line, but they could turn out to be ineffective after all costs are taken into account. Optimal marketing volatility needs to trade off sales effectiveness and extra costs resulting from marketing volatility.This paper was accepted by Pradeep K. Chintagunta, marketing.

Structural colors of 2D gratings are iridescent, color-tunable, and never fade, which renders them appealing for anti-counterfeiting applications. However, for advanced security, it still remains a challenge to completely hide the encrypted color patterns and reveal them on demand. In this work, a water-responsive photonic grating consisting of a micropillar array and a hydrogel overcoat with a similar refractive index, termed “hydrocipher”, is presented. The joint effect of stimuli-reversible refractive-index (mis)match and reconfigurable grating-based diffraction coloration enables a complete encryption of the structural color and rapid decryption. The photonic structure shows a strong iridescence due to the angle-dependent diffraction when the hydrogel overcoat is swollen from water. Upon drying, the micropillars bend and the refractive index contrast disappears, which dramatically lessens the diffraction intensity and renders the surface highly transparent. The dehydrated-to-hydrated state transition can occur within 1 s, enabling fast decryption. The color switching is highly reversible over a prolonged hydration/dehydration cycle, and the dehydrated hydrogel layer protects the delicate micropillar array from external mechanical stress. The creative combination of hydrogel material and the 2D grating structure offers a new and simple strategy for realizing reversible, durable, and fast-response cryptography with potentially broad impact on the anti-counterfeiting technology market.

Differentiation and activation of osteoclasts play a key role in the development of musculoskeletal diseases as these cells are primarily involved in bone resorption. Osteoclasts can be generated in vitro from monocyte/macrophage precursor cells in the presence of certain cytokines, which promote survival and differentiation. Here, both in vivo and in vitro techniques are demonstrated, which allow scientists to study different cytokine contributions towards osteoclast differentiation, signaling, and activation. The minicircle DNA delivery gene transfer system provides an alternative method to establish an osteoporosis-related model is particularly useful to study the efficacy of various pharmacological inhibitors in vivo. Similarly, in vitro culturing protocols for producing osteoclasts from human precursor cells in the presence of specific cytokines enables scientists to study osteoclastogenesis in human cells for translational applications. Combined, these techniques have the potential to accelerate drug discovery efforts for osteoclast-specific targeted therapeutics, which may benefit millions of osteoporosis and arthritis patients worldwide.

BACKGROUND/AIMS: The adenoma detection rate (ADR) does not reflect the complete detection of every adenoma during colonoscopy; thus, many surrogate indicators have been suggested. This study investigated whether the ADR and surrogate quality indicators reflect the adenoma miss rate (AMR) when performing qualified colonoscopy. METHODS: We performed a prospective, multicenter, cross-sectional study of asymptomatic examinees aged 50 to 75 years who underwent back-to-back screening colonoscopies by eight endoscopists. The ADR and surrogate quality indicators, including polyp detection rate, total number of adenomas per colonoscopy, additional adenomas found after the first adenoma per colonoscopy (ADR-Plus), and total number of adenomas per positive participant, were calculated for the prediction of AMR. RESULTS: A total of 371 back-to-back colonoscopies were performed. There was a significant difference in ADRs (range, 44% to 75.4%; p=0.024), polyp detection rates (range, 56% to 86.9%; p=0.008) and adenomas per positive participants (range, 1.19 to 2.30; p=0.038), and a tendency of a difference in adenomas per colonoscopy (range, 0.62 to 1.31; p=0.051) and ADR-Plus (range, 0.13 to 0.70; p=0.054) among the endoscopists. The overall AMR was 20.1%, and AMRs were not different (range, 13.9 to 28.6; p>0.05) among the endoscopists. No quality indicators were significantly correlated with AMR. The number of adenomas found during the first colonoscopy was an independent factor for increased AMR (odds ratio, 1.79; p<0.001). CONCLUSIONS: The colonoscopy quality indicators were significantly different among high-ADR endoscopists, and none of the quality indicators reflected the AMR of good quality colonoscopy performances. The only factor influencing AMR was the number of adenomas detected during colonoscopy.

Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates^1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called encephalopathy of prematurity³. Over 80% of infants born before post-conception week 25 have moderate-to-severe long-term neurodevelopmental impairments⁴. The susceptible cell types in the cerebral cortex and the molecular mechanisms underlying associated gray-matter defects in premature infants remain unknown. Here we used human three-dimensional brain-region-specific organoids to study the effect of oxygen deprivation on corticogenesis. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and showed that these are related to the unfolded protein response and changes. Moreover, we verified these findings in human primary cortical tissue and demonstrated that a small-molecule modulator of the unfolded protein response pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be valuable for studying the environmental and genetic factors underlying injury in the developing human brain.