Sample Size Estimation Based on Event Data for a Two-Stage Survival Adaptive Trial with Different Durations

In clinical development, an adaptive design combining results from two separate studies (e.g., a seamless adaptive design with a dose finding study phase and a confirmatory study phase) is commonly considered. The purpose of an adaptive design is not only to reduce lead time between the two studies, but also to evaluate the treatment effect in a more efficient way. In this paper, the focus is on the case where the study objectives are the same but the time durations of the study periods are different in the two stages. In particular, event data are collected in both stages. Statistical procedure for combining data observed from the two different stages is discussed. Furthermore, results on hypotheses testing and sample size calculation are derived for the comparison of two treatments.     

数字化塑形钛网在颅骨缺损修补术中的临床运用

目的：探讨数字化塑形钛网修补颅骨缺损的临床治疗效果。方法对我院2010年8月~2013年9月收治的46例需进行颅骨缺损手术的患者行数字化塑形钛网修补术，比较同期的42例行传统手工塑形钛网颅骨修补术的患者手术质量和术后恢复情况。进行6个月的术后随访，统计评估患者术后恢复情况。结果与传统手术方法相比，数字化塑形钛网修补手术在用时、并发症发生情况等方面优势明显（P＜0.01），术后功能状态评分和生活质量评分差异无统计学意义（P＞0.05）。结论数字化塑形钛网技术在颅骨缺损的修复治疗上具有塑形美观、术后恢复效果好，可减少手术时间等诸多优点，是在条件允许的情况下的首选手术方式。     

Fossilized Venom: The Unusually Conserved Venom Profiles of Heloderma Species (Beaded Lizards and Gila Monsters)

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation.     

Economic repercussions of fisheries-induced evolution

Fish stocks experiencing high fishing mortality show a tendency to mature earlier and at a smaller size, which may have a genetic component and therefore long-lasting economic and biological effects. To date, the economic effects of such ecoevolutionary dynamics have not been empirically investigated. Using 70 y of data, we develop a bioeconomic model for Northeast Arctic cod to compare the economic yield in a model in which life-history traits can vary only through phenotypic plasticity with a model in which, in addition, genetic changes can occur. We find that evolutionary changes toward faster growth and earlier maturation occur consistently even if a stock is optimally managed. However, if a stock is managed optimally, the evolutionary changes actually increase economic yield because faster growth and earlier maturation raise the stock’s productivity. The optimal fishing mortality is almost identical for the evolutionary and nonevolutionary model and substantially lower than what it has been historically. Therefore, the costs of ignoring evolution under optimal management regimes are negligible. However, if fishing mortality is as high as it has been historically, evolutionary changes may result in economic losses, but only if the fishery is selecting for medium-sized individuals. Because evolution facilitates growth, the fish are younger and still immature when they are susceptible to getting caught, which outweighs the increase in productivity due to fish spawning at an earlier age.     

Characteristics of Individuals With Toileting Problems and Intellectual Disability Using the Profile of Toileting Issues (POTI)

The prevalence of toileting problems was assessed in 153 adults with intellectual disability (ID) using the Profile of Toileting Issues (POTI) and comparisons were made based on various demographic variables. The most frequently endorsed problems were “has toileting accidents during the day,” “has toileting accidents during the night,” “has wet underwear in the past month,” “requires the use of fiber supplements/laxatives to defecate,” and “is on a medication with a known side effect of constipation.” The least frequently endorsed problems were “others tease the individual about accident odor” and “individual is rejected by peers due to toileting problems.” Based on overall POTI scores, significant between-group differences were found for verbal ability, ambulatory ability, use of fiber or laxatives, and level of ID. Results and implications are discussed.     

Comparison of Long-Term Biocompability of PVDF and PP Meshes

ABSTRACT

Background: Abdominal hernia repair is the most frequently performed operation in surgery. Mesh repair in hernia surgery has become an integral component. Although meshes made of PVDF are already in clinical use, so far no data of long-term biocompability are available. Methods: In this study a PVDF mesh was compared to a polypropylene mesh with regard to its long-term biocompatibility. A total of 28 rats were randomized to two groups. Mesh material was implanted subcutaneously; animals were euthanized seven days and six months postoperatively. The quantity of inflammatory tissue response was characterized by measuring the diameter of the foreign body granuloma. Furthermore quality of cellular immune response (T-lymphocytes, macrophages, and neutrophils), and inflammation (COX-2) was analyzed by immunohistochemistry. Furthermore the collagen type I/III ratio was determined. Results: Macrophages, T-lymphocytes, neutrophiles, and COX-2 declined significantly up to six months postoperatively in comparison to day 7 for both PVDF and PP meshes, and in both groups the collagen ratio increased significantly in the course of time. PVDF meshes showed a foreign body granuloma size significantly reduced compared to PP (7 days: 20 ± 2 μm vs. 27 ± 2 μm; 6 months 15 ± 2 μm vs. 22 ± 3 μm; p < .001). However no significant differences were found analyzing cellular response six months postoperatively. Conclusions: Our current data suggest that even in the long-term course after six months and despite a higher effective surface of the PVDF samples it showed a smaller foreign body granuloma than with PP whereas the cellular response was similar.     

Mechanisms of liver involvement in systemic disease

The liver may be injured during the course of many systemic diseases. The mechanisms of injury can be broadly divided into four pathways: vascular, toxic, immune, and hormonal. Vascular obstruction may be an early event but is also the late common pathway from all mechanisms. Despite the large number of possible initiating factors, the end results are few, including death of hepatocytes or cholangiocytes, leading to the stereotyped syndromes of acute liver failure, non-cirrhotic portal hypertension, or cirrhosis. This small number of outcomes is a reflection of the few anatomic patterns that can be generated by microvascular obstruction. Vascular obstruction may occur by thrombosis, inflammation, or congestive injury. The innate immunity pathway is activated by endotoxin and other agents, leading to inflammatory infiltration, release of cytokines and reactive oxygen species, and necrosis. The adaptive immune pathway involves the generation of antibodies and antigen-specific cell-mediated attack on hepatic cells. Hormonal effects are principally involved when overnutrition leads to hyperinsulinemia followed by hepatocellular necrosis.