Systematic identification of cis-silenced genes by trans complementation

A gene’s transcriptional output is the combined product of two inputs: diffusible factors in the cellular milieu acting in trans, and chromatin state acting in cis. Here, we describe a strategy for dissecting the relative contribution of cis versus trans mechanisms to gene regulation. Referred to as trans complementation, it entails fusing two disparate cell types and searching for genes differentially expressed between the two genomes of fused cells. Any differential expression can be causally attributed to cis mechanisms because the two genomes of fused cells share a single homogenized milieu in trans. This assay uncovered a state of transcriptional competency that we termed ‘occluded’ whereby affected genes are silenced by cis-acting mechanisms in a manner that blocks them from responding to the trans-acting milieu of the cell. Importantly, occluded genes in a given cell type tend to include master triggers of alternative cell fates. Furthermore, the occluded state is maintained during cell division and is extraordinarily stable under a wide range of physiological conditions. These results support the model that the occlusion of lineage-inappropriate genes is a key mechanism of cell fate restriction. The identification of occluded genes by our assay provides a hitherto unavailable functional readout of chromatin state that is distinct from and complementary to gene expression status

The Economics of Collective Brands

We consider the consequences of a shared brand name such as geographical names used to identify high quality products, for the incentives of otherwise autonomous firms to invest in quality. We contend that such collective brand labels improve communication between sellers and consumers, when the scale of production is too small for individual firms to establish reputations on a stand alone basis. This has two opposing effects on member firms' incentives to invest in quality. On the one hand, it increases investment incentives by increasing the visibility and transparency of individual member firms, which increases the return from investment in quality. On the other hand, it creates an incentive to free ride on the group's reputation, which can lead to less investment in quality. We identify parmater values under which collective branding delivers higher quality than is achievable by stand alone firms

Overestimation of Oxygen Saturation Measured by Pulse Oximetry in Hypoxemia. Part 1: Effect of Optical Pathlengths-Ratio Increase

On average, arterial oxygen saturation measured by pulse oximetry (SpO2) is higher in hypoxemia than the true oxygen saturation measured invasively (SaO2), thereby increasing the risk of occult hypoxemia. In the current article, measurements of SpO2 on 17 cyanotic newborns were performed by means of a Nellcor pulse oximeter (POx), based on light with two wavelengths in the red and infrared regions (660 and 900 nm), and by means of a novel POx, based on two wavelengths in the infrared region (761 and 820 nm). The SpO2 readings from the two POxs showed higher values than the invasive SaO2 readings, and the disparity increased with decreasing SaO2. SpO2 measured using the two infrared wavelengths showed better correlation with SaO2 than SpO2 measured using the red and infrared wavelengths. After appropriate calibration, the standard deviation of the individual SpO2−SaO2 differences for the two-infrared POx was smaller (3.6%) than that for the red and infrared POx (6.5%, p 2 readings in hypoxemia was explained by the increase in hypoxemia of the optical pathlengths-ratio between the two wavelengths. The two-infrared POx can reduce the overestimation of SpO2 measurement in hypoxemia and the consequent risk of occult hypoxemia, owing to its smaller increase in pathlengths-ratio in hypoxemia

Emergency Colectomies in the Elderly Population—Perioperative Mortality Risk-Factors and Long-Term Outcomes

Background: As the population ages emergency surgeries among the elderly population, including colonic resections, is also increasing. Data regarding the short- and long-term outcomes in this population is scarce. Methods: A retrospective study was performed to investigate mortality and mortality risk factors associated with emergent colectomies in older compared to younger patients in a single university affiliated tertiary hospital. Patients with metastatic disease, colectomy due to trauma or index colectomy within 30 days prior to emergent surgery were excluded. Results: Operative outcomes compared among age groups, included 30-day mortality, mortality risk-factors and long-term survival. 613 eligible patients were included in the cohort. Mean age was 69.4 years, 45.1% were female. Patients were divided into four age groups: 18–59, 60–69, 70–79 and ≥80-years. Thirty-day mortality rates were 3.2%, 11%, 29.3% and 37.8%, respectively and 22% for the entire cohort. Risk-factors for perioperative death in the younger group were related to severity of ASA score and WBC count. In groups 60–69, 70–79, main risk-factors were ADL dependency and ASA score. In the ≥80 group, risk-factors affecting perioperative mortality, included ASA score, pre-operative albumin, creatinine, WBC levels, cancer etiology, ADL dependency, and dementia. Long-term survival differed significantly between age groups. Conclusion: Perioperative mortality with emergency colectomy increases with patients’ age. Patients older than eighty-years undergoing urgent colectomies have extremely high mortality rates, leading to a huge burden on medical services. Evaluating risk-factors for mortality and pre-operative discussion with patients and families is important. Screening the elderly population for colonic pathologies can result in early diagnosis potentially leading to elective surgeries with decreased mortality