Inventory Investment, Internal-Finance Fluctuation, and the Business Cycle

macroeconomics, inventory investment, internal-finance fluctuation, business cycle

Understanding an Organization and Developing the Web Site

Web site developers frequently become captivated with technology and ignore the needs of the users while developing web sites. This can result in confusing user interfaces, unstructured information, and improper content. Once a web site is in place it can be very costly to redesign and time consuming to redesign it. This paper analyzes the principles of web site design and the design of public sector web sites. Research shows that as citizens use the web with increasing frequency, redesigning a web site can make it more accessible, usable, and engaging. Other studies on web site design demonstrate that the proper use of navigational tools can also improve the user experience. To show the practical application of the principles discussed the information needs of the Orange County Recreation and Parks Department are studied. The study consists of a stakeholder analysis, user analysis, information analysis, prototype design, and prototype redesign

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Estimating the Comparative Effectiveness of Feeding Interventions in the Pediatric Intensive Care Unit: A Demonstration of Longitudinal Targeted Maximum Likelihood Estimation.

Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008-2011). We estimate the probability of a child's being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime "never feed" are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime "feed from day 3," the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use

Salinity and time can alter epibacterial communities of an invasive seaweed

The establishment of epibacterial communities is fundamental to seaweed health, and fitness, in modulating ecological interactions and may also facilitate adaptation to new environments. Few recent studies have investigated the influence of abiotic factors like light, temperature as drivers of epibacterial community composition on seaweeds. Although salinity can determine bacterial abundance, growth and community composition, influence of salinity as a driver of epibacterial community composition (until species level) has not been investigated for seaweeds and especially under long time scales. We also do not know how abiotic stressors may influence the ‘core’ bacterial species of seaweeds. Following an initial (immediately after field collection, T0) sampling of epibacterial community of an invasive red seaweed Agarophyton vermicullophylum, we conducted a long term mesocosm experiment for 5 months, to examine the influence of three different salinities (low, medium and high) at two different time points (T1, T2) on the epibacterial community richness and composition of Agarophyton. Metagenomic sequencing showed that epibacterial communities changed significantly according to salinity and time points sampled. Epibacterial richness was significantly different between low and high salinities at both time points. Epibacterial richness also varied significantly among T1 and T2 within low, medium and high salinity level. Irrespective of salinity levels and time points sampled 727 taxa consistently appeared in all Agarophyton samples hinting at the presence of core bacterial species on the surface of the alga. Our results indicate that both salinity and time can be major driving forces in structuring epibacterial communities of seaweeds with respect to richness and β diversity. We highlight the necessity of conducting long term experiments allowing us to detect and understand epibacterial succession over time on seaweeds

Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

INTRODUCTION: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm(2) versus 12.5–15.7 cm(2)). STUDY DESIGN AND METHODS: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A). In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF) filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B). RESULTS: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo. CONCLUSION: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of experimental pain models is critical to the advancement of translational pain research

Localized Ca2+ uncaging reveals polarized distribution of Ca2+-sensitive Ca2+ release sites: mechanism of unidirectional Ca2+ waves

Ca2+-induced Ca2+ release (CICR) plays an important role in the generation of cytosolic Ca2+ signals in many cell types. However, it is inherently difficult to distinguish experimentally between the contributions of messenger-induced Ca2+ release and CICR. We have directly tested the CICR sensitivity of different regions of intact pancreatic acinar cells using local uncaging of caged Ca2+. In the apical region, local uncaging of Ca2+ was able to trigger a CICR wave, which propagated toward the base. CICR could not be triggered in the basal region, despite the known presence of ryanodine receptors. The triggering of CICR from the apical region was inhibited by a pharmacological block of ryanodine or inositol trisphosphate receptors, indicating that global signals require coordinated Ca2+ release. Subthreshold agonist stimulation increased the probability of triggering CICR by apical uncaging, and uncaging-induced CICR could activate long-lasting Ca2+ oscillations. However, with subthreshold stimulation, CICR could still not be initiated in the basal region. CICR is the major process responsible for global Ca2+ transients, and intracellular variations in sensitivity to CICR predetermine the activation pattern of Ca2+ waves