Beyond Problems and Cases: Discussion Materials for Accounting in Executive Programs Business School

Selection or development of classroom materials for an accounting class in an executive program is complicated by the fact that some students enter the program with a substantial knowledge of accounting while others may have no background at all. Furthermore, general management programs do not usually focus on making all students equally knowledgeable about what accountants do and how to use the information that accounting provides. Problems and cases are sometimes not successful as discussion materials in the mixed audience class because some students are not challenged while others are overwhelmed because of their lack of exposure to the methods and principles of accounting. We describe a new class of materials prepared for executive program accounting classes that are based on contemporary events that become the bases for informed discussion among students where learning takes place at each student’s level while working in small groups to understand the problems, possible solutions, and actions that might be taken to clarify issues and solutions to the problems posed. Three examples are described and illustrated

DNA-coated Functional Oil Droplets

Many industrial soft materials often include oil-in-water (O/W) emulsions at the core of their formulations. By using tuneable interface stabilizing agents, such emulsions can self-assemble into complex structures. DNA has been used for decades as a thermoresponsive highly specific binding agent between hard and, recently, soft colloids. Up until now, emulsion droplets functionalized with DNA had relatively low coating densities and were expensive to scale up. Here a general O/W DNA-coating method using functional non-ionic amphiphilic block copolymers, both diblock and triblock, is presented. The hydrophilic polyethylene glycol ends of the surfactants are functionalized with azides, allowing for efficient, dense and controlled coupling of dibenzocyclooctane functionalized DNA to the polymers through a strain-promoted alkyne-azide click reaction. The protocol is readily scalable due to the triblock's commercial availability. Different production methods (ultrasonication, microfluidics and membrane emulsification) are used with different oils (hexadecane and silicone oil) to produce functional droplets in various size ranges (sub-micron, $\sim 20\,\mathrm{\mu m}$ and $> 50\,\mathrm{\mu m}$), showcasing the generality of the protocol. Thermoreversible sub-micron emulsion gels, hierarchical "raspberry" droplets and controlled droplet release from a flat DNA-coated surface are demonstrated. The emulsion stability and polydispersity is evaluated using dynamic light scattering and optical microscopy. The generality and simplicity of the method opens up new applications in soft matter and biotechnological research and industrial advances.Comment: 7 pages, 2 figures, 1 tabl

Ex^2Box: Interdependent Modes of Binding in a Two-Nanometer-Long Synthetic Receptor

Incorporation of two biphenylene-bridged 4,4′-bipyridinium extended viologen units into a para-phenylene-based cyclophane results in a synthetic receptor that is 2 nm long and adopts a box-like geometry. This cyclophane, Ex^2Box^4+, possesses the ability to form binary and ternary complexes with a myriad of guest molecules ranging from long π-electron-rich polycyclic aromatic hydrocarbons, such as tetracene, tetraphene, and chrysene, to π-electron-poor 2,6-dinitrotoluene, 1,2,4-trichlorobenzene, and both the 9,10- and 1,4-anthraquinone molecules. Moreover, Ex^2Box^4+ is capable of forming one-to-one complexes with polyether macrocycles that consist of two π-electron-rich dioxynaphthalene units, namely, 1,5-dinaphtho[38]crown-10. This type of broad molecular recognition is possible because the electronic constitution of Ex^2Box^4+ is such that the pyridinium rings located at the “ends” of the cyclophane are electron-poor and prefer to enter into donor–acceptor interactions with π-electron-rich guests, while the “middle” of the cyclophane, consisting of the biphenylene spacer, is more electron-rich and can interact with π-electron-poor guests. In some cases, these different modes of binding can act in concert to generate one-to-one complexes which possess high stability constants in organic media. The binding affinity of Ex^2Box^4+ was investigated in the solid state by way of single-crystal X-ray diffraction and in solution by using UV–vis and NMR spectroscopy for 12 inclusion complexes consisting of the tetracationic cyclophane and the corresponding guests of different sizes, shapes, and electronic compositions. Additionally, density functional theory was carried out to elucidate the relative energetic differences between the different modes of binding of Ex^2Box^4+ with anthracene, 9,10-anthraquinone, and 1,4-anthraquinone in order to understand the degree with which each mode of binding contributes to the overall encapsulation of each guest

Cathepsin D Expression and Gemcitabine Resistance in Pancreatic Cancer.

BackgroundCathepsin-D (CatD), owing to its dual role as a proteolytic enzyme and as a ligand, has been implicated in cancer progression. The role of CatD in pancreatic ductal adenocarcinoma is unknown.MethodsCatD expression quantified by immunohistochemistry of tumor-tissue microarrays of 403 resected pancreatic cancer patients from the ESPAC-Tplus trial, a translational study within the ESPAC (European Study Group for Pancreatic Cancer) trials, was dichotomously distributed to low and high H scores (cut off 22.35) for survival and multivariable analysis. The validation cohort (n = 69) was recruited based on the hazard ratio of CatD from ESPAC-Tplus. 5-fluorouracil-, and gemcitabine-resistant pancreatic cancer cell lines were employed for mechanistic experiments. All statistical tests were two-sided.ResultsMedian overall survival was 23.75 months and median overall survival for patients with high CatD expression was 21.09 (95% confidence interval [CI] = 17.31 to 24.80) months vs 27.20 (95% CI = 23.75 to 31.90) months for low CatD expression (χ2 LR, 1DF = 4.00; P = .04). Multivariable analysis revealed CatD expression as a predictive marker in gemcitabine-treated (z stat = 2.33; P = .02) but not in 5-fluorouracil-treated (z stat = 0.21; P = .82) patients. An independent validation cohort confirmed CatD as a negative predictive marker for survival (χ2 LR, 1DF = 6.80; P = .009) and as an independent predictive marker in gemcitabine-treated patients with a hazard ratio of 3.38 (95% CI = 1.36 to 8.38, P = .008). Overexpression of CatD was associated with a concomitant suppression of the acid sphingomyelinase, and silencing of CatD resulted in upregulation of acid sphingomyelinase with rescue of gemcitabine resistance.ConclusionsAdjuvant gemcitabine is less effective in pancreatic ductal adenocarcinoma with high CatD expression, and thus CatD could serve as a marker for biomarker-driven therapy

Three Thousand Years of Continuity in the Maternal Lineages of Ancient Sheep (Ovis aries) in Estonia

lthough sheep (Ovis aries) have been one of the most exploited domestic animals in Estonia since the Late Bronze Age, relatively little is known about their genetic history. Here, we explore temporal changes in Estonian sheep populations and their mitochondrial genetic diversity over the last 3000 years. We target a 558 base pair fragment of the mitochondrial hypervariable region in 115 ancient sheep from 71 sites in Estonia (c. 1200 BC – AD 1900s), 19 ancient samples from Latvia, Russia, Poland and Greece (6800 BC – AD 1700), as well as 44 samples of modern Kihnu native sheep breed. Our analyses revealed: (1) 49 mitochondrial haplotypes, associated with sheep haplogroups A and B; (2) high haplotype diversity in Estonian ancient sheep; (3) continuity in mtDNA haplotypes through time; (4) possible population expansion during the first centuries of the Middle Ages (associated with the establishment of the new power regime related to 13th century crusades); (5) significant difference in genetic diversity between ancient populations and modern native sheep, in agreement with the beginning of large-scale breeding in the 19th century and population decline in local sheep. Overall, our results suggest that in spite of the observed fluctuations in ancient sheep populations, and changes in the natural and historical conditions, the utilisation of local sheep has been constant in the territory of Estonia, displaying matrilineal continuity from the Middle Bronze Age through the Modern Period, and into modern native sheep

Mechanical Bonds and Topological Effects in Radical Dimer Stabilization

While mechanical bonding stabilizes tetrathiafulvalene (TTF) radical dimers, the question arises: what role does topology play in catenanes containing TTF units? Here, we report how topology, together with mechanical bonding, in isomeric [3]- and doubly interlocked [2]catenanes controls the formation of TTF radical dimers within their structural frameworks, including a ring-in-ring complex (formed between an organoplatinum square and a {2+2} macrocyclic polyether containing two 1,5-dioxynaphthalene (DNP) and two TTF units) that is topologically isomeric with the doubly interlocked [2]catenane. The separate TTF units in the two {1+1} macrocycles (each containing also one DNP unit) of the isomeric [3]catenane exhibit slightly different redox properties compared with those in the {2+2} macrocycle present in the [2]catenane, while comparison with its topological isomer reveals substantially different redox behavior. Although the stabilities of the mixed-valence (TTF2)^(•+) dimers are similar in the two catenanes, the radical cationic (TTF^(•+))_2 dimer in the [2]catenane occurs only fleetingly compared with its prominent existence in the [3]catenane, while both dimers are absent altogether in the ring-in-ring complex. The electrochemical behavior of these three radically configurable isomers demonstrates that a fundamental relationship exists between topology and redox properties

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk