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Do you sometimes feel stuck as a leader, while at other times everything seems effortless? The explanation often lies in your own psychological state. When you’re in the zone, you express yourself naturally, venture beyond the familiar to pursue ambitious goals, embody your highest values, and embrace learning—and can accomplish extraordinary things. But four common stumbling blocks can prevent you from entering it: the misperceptions that there are no alternatives, that there is no hope, that there is no time, and that there is no need for leadership. Those misperceptions can be overcome, however, if you ask the right questions and follow a handful of practices designed to open your mind to a world of possibilities. [ABSTRACT FROM AUTHOR]

Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development1, metabolism2, 3–4, immune responses5, 6–7and cognitive function8. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear9,10. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA–methylcysteamine (BA–MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues. This host-dependent MCY conjugation inverts BA function in the hepatobiliary system. Whereas microbiota-derived free BAs function as agonists of the farnesoid X receptor (FXR) and negatively regulate BA production, BA–MCYs act as potent antagonists of FXR and promote expression of BA biosynthesis genes in vivo. Supplementation with stable-isotope-labelled BA–MCY increased BA production in an FXR-dependent manner, and BA–MCY supplementation in a mouse model of hypercholesteraemia decreased lipid accumulation in the liver, consistent with BA–MCYs acting as intestinal FXR antagonists. The levels of BA–MCY were reduced in microbiota-deficient mice and restored by transplantation of human faecal microbiota. Dietary intervention with inulin fibre further increased levels of both free BAs and BA–MCY levels, indicating that BA–MCY production by the host is regulated by levels of microbiota-derived free BAs. We further show that diverse BA–MCYs are also present in human serum. Together, our results indicate that BA–MCY conjugation by the host balances host-dependent and microbiota-dependent metabolic pathways that regulate FXR-dependent physiology.

Chronic kidney disease, defined as abnormalities of kidney structure or function for more than 3 months, (1) is associated with an increased risk of kidney failure and cardiovascular events. (2,3) [...], BACKGROUND: Guidelines recommend nephrology referral for people with advanced non-dialysis-dependent chronic kidney disease, based mostly on survival benefits seen in retrospective studies of dialysis patients, which may not be generalizable to the broader population with chronic kidney disease. We aimed to examine the association between outpatient nephrology consultation and survival in adults with stage 4 chronic kidney disease. METHODS: We linked population-based laboratory and administrative data from 2002 to 2014 in Alberta, Canada, on adults with stage 4 chronic kidney disease (sustained estimated glomerular filtration rate [greater than or equal to] 15 to < 30 mL/min/1.73 [m.sup.2] for > 90 d), who had never had kidney failure and had had no outpatient nephrology encounter in the 2 years preceding study entry. Participants who had never had an outpatient nephrology visit before renal replacement treatment were considered "unexposed." Participants who saw a nephrologist during follow-up were considered "unexposed" before the first outpatient nephrology visit and "exposed" thereafter. The primary outcome was all-cause mortality. RESULTS: Of the 14382 study participants (median follow-up 2.7 yr), 64% were aged [greater than or equal to] 80 years, 35% saw a nephrologist and 66% died during follow-up. Nephrology consultation was associated with lower mortality (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82-0.93). The association was strongest in people < 70 years (HR 0.78, 95% CI, 0.65-0.92), progressively weaker with increasing age, and absent in people [greater than or equal to] 90 years (HR 1.05, 95% CI 0.88-1.25). INTERPRETATION: The survival benefit of nephrology consultation in adults with stage 4 chronic kidney disease may be smaller than expected and appears to attenuate with increasing age. These findings should inform recommendations for nephrology referral considering the advanced age of the patient population meeting current referral criteria.

Bile acids (BAs) are steroid detergents in bile that contribute to the absorption of fats and fat-soluble vitamins while shaping the gut microbiome because of their antimicrobial properties1–4. Here we identify the enzyme responsible for a mechanism of BA metabolism by the gut microbiota involving amino acid conjugation to the acyl-site of BAs, thus producing a diverse suite of microbially conjugated bile acids (MCBAs). We show that this transformation is mediated by acyltransferase activity of bile salt hydrolase (bile salt hydrolase/transferase, BSH/T). Clostridium perfringensBSH/T rapidly performed acyl transfer when provided various amino acids and taurocholate, glycocholate or cholate, with an optimum at pH 5.3. Amino acid conjugation by C. perfringensBSH/T was diverse, including all proteinaceous amino acids except proline and aspartate. MCBA production was widespread among gut bacteria, with strain-specific amino acid use. Species with similar BSH/T amino acid sequences had similar conjugation profiles and several bsh/talleles correlated with increased conjugation diversity. Tertiary structure mapping of BSH/T followed by mutagenesis experiments showed that active site structure affects amino acid selectivity. These MCBA products had antimicrobial properties, where greater amino acid hydrophobicity showed greater antimicrobial activity. Inhibitory concentrations of MCBAs reached those measured natively in the mammalian gut. MCBAs fed to mice entered enterohepatic circulation, in which liver and gallbladder concentrations varied depending on the conjugated amino acid. Quantifying MCBAs in human faecal samples showed that they reach concentrations equal to or greater than secondary and primary BAs and were reduced after bariatric surgery, thus supporting MCBAs as a significant component of the BA pool that can be altered by changes in gastrointestinal physiology. In conclusion, the inherent acyltransferase activity of BSH/T greatly diversifies BA chemistry, creating a set of previously underappreciated metabolites with the potential to affect the microbiome and human health.

There is widespread interest in expanding the uptake of home dialysis in North America. Although kidney transplantation should be the preferred option in eligible patients, home hemodialysis (HD) and peritoneal dialysis (PD) offer cost-effective options for KRT. In this review, the motivation for promoting home dialysis is presented, and the literature supporting it is critically reviewed. Randomized comparisons of home HD and PD with in-center HD have been challenging to conduct and provide only limited information. Nonrandomized studies are heterogeneous in their design and have often yielded conflicting results. They are prone to bias, and this must be carefully considered when evaluating this literature. Home modalities seem to have equivalent clinical outcomes and quality of life when compared with in-center HD. However, the cost of providing home therapies, particularly PD, is lower than conventional, in-center HD. Measures of home dialysis utilization, the philosophy behind their measurement, and important factors to consider when interpreting them are discussed. The importance of understanding measures of home dialysis utilization in the context of rates of kidney failure, the proportion of individuals who opt for conservative care, and rates of kidney transplantation is highlighted, and a framework for proposing targets is presented, using PD as an example.

Each year, the Recommendations Task Force of the Canadian Hypertension Education Program updates its recommendations for the diagnosis and treatment of hypertension in Canada. During the past two years, the [...]

The intestinal microbiota is an important regulator of bone health. In previous studies we have shown that intestinal microbiota dysbiosis, induced by treatment with broad spectrum antibiotics (ABX) followed by natural repopulation, results in gut barrier dysfunction and bone loss. We have also shown that treatment with probiotics or a gut barrier enhancer can inhibit dysbiosis-induced bone loss. The overall goal of this project was to test the effect of Korean Red Ginseng (KRG) extract on bone and gut health using antibiotics (ABX) dysbiosis-induced bone loss model in mice.

Initiating chronic dialysis has major implications for patients and health care systems. Within the spectrum of severity of chronic kidney disease, there is a need to identify a threshold before [...]

When employees are disengaged and underperforming, the reaction of many managers is to try new incentives and ratchet up oversight and control. Yet often nothing improves. Why? Because the assumption behind such conventional approaches is that work is fundamentally contractual and that employees are self-interested agents who will seek to minimize personal effort. And that assumption becomes a self-fulfilling prophecy: Employees do just what is needed to earn a reward or meet a standard, and nothing more. But there is another way: Rally the organization behind an authentic higher purpose—an aspirational mission that explains how employees are making a difference and gives them a sense of meaning. If you do that, they will try new things, move into deep learning, and make surprising contributions. The workforce will become energized and committed, and performance will climb. In this article, Quinn and Thakor describe how organizations like DTE Energy, KPMG, and Sandler O’Neill have dramatically increased employee engagement after discovering their higher purposes. The authors outline eight steps other companies can follow to break free of the conventional thinking about worker motivation, help a higher purpose permeate decisions throughout the company, and set off a positive chain of events. INSET: HOW TO DO IT.. [ABSTRACT FROM AUTHOR]

The debate about appropriate blood pressure targets for patients with hypertension and diabetes is of substantial public health importance because the global burden of diabetes and hypertension is large and [...]

IN CHINA, students and scholars are being imprisoned by the Communist Party at 're-education camps.' In Sudan, authorities are beating and tear-gassing students participating in protests. And as Brazil reels [...]

Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n?=?24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing. However, two outcomes that were not predicted when antibiotics were applied were 5) community profile shifts with little change in total bacterial load (TBL), and 6) increases in TBL. The latter outcome was observed in 17.8% of samples with a TBL increase of greater than 20% and 6.8% of samples with an increase greater than 40%, demonstrating significant increases in community carrying capacity in the presence of an antibiotic. An iteration of the mathematical model showed that TBL increase was due to antibiotic-mediated release of pH-dependent inhibition of pathogens by anaerobe fermentation. These dynamics were verified in vitro when killing of fermenters resulted in a higher community carrying capacity compared to a no antibiotic control. Metagenomic sequencing of sputum samples during antibiotic therapy revealed similar dynamics in clinical samples. This study shows that the complex microbial ecology dictates the outcomes of antibiotic therapy against a polymicrobial infection.

Each year tax collectors and circuit court clerks across the state conduct tax deed sales to collect unpaid ad valorem real property taxes. Occasionally, successful bidders at these sales acquire [...]

Background: Providing support is important to maintain a patient on peritoneal dialysis (PD), though its impact on outcomes has not been investigated thoroughly. We examined the association between having support and risk of a transfer to hemodialysis.Methods: In this retrospective observational cohort study, we used data captured in the Dialysis Measurement Analysis and Reporting system about patients who started PD in Alberta, Canada, between 1 January 2013 and 30 September 2018. Support was defined as the availability of a support person in the home who was able, willing and available to provide support for PD in the patient’s residence. The outcome of interest was a transfer to hemodialysis for at least 90 days. We estimated the cumulative incidence of a transfer over time accounting for competing risks and hazard ratios to summarise the association between support and a transfer. We split follow-up time as hazard ratios varied over time.Results: Six hundred and eighty-three incident PD patients, median age 58 years (IQR: 47–68) and 35% female, were followed for a median of 15 months. The cumulative incidence of a transfer to hemodialysis at 24 months was 26%. Having support was associated with a reduced risk of a transfer between 3 and 12 months after the start of dialysis (HR3-12mo: 0.44; 95% CI: 0.25–0.78), but not earlier (hazard ratio (HR)<3mo: 0.96; 95% confidence interval (CI): 0.55–1.69) or later (HR>12mo: 1.19; 95% CI: 0.65–2.17).Conclusions: A transfer to hemodialysis is common. Having a support person at home is associated with a short-term protective effect after the initiation of PD.

Albumin-to-creatinine ratio (ACR), the preferred method to quantify proteinuria, can be calculated from urine dipstick protein or protein-to-creatinine ratio (PCR). The performance of calculated vs. measured ACR in predicting kidney failure and death without kidney failure in people with chronic kidney disease (CKD) is unknown. Here, we used population-based data from Alberta, Canada, to identify adults with incident moderate-severe CKD (sustained for more than 90 days) from 2008-04-01 to 2017-03-31, who had same-day measures of ACR and urine dipstick (ACR-dipstick cohort) or PCR (ACR-PCR cohort) in the two years before cohort entry. We followed participants until 2019-03-31 and trained competing risk models of kidney failure and death without kidney failure including age, sex, estimated glomerular filtration rate, diabetes, cardiovascular disease, and either measured or calculated ACR. Model performance was tested in cohorts created using the same algorithm in Manitoba, Canada. The ACR-dipstick and ACR-PCR cohorts included 18,731 and 4,542 people (training cohorts) and 821 and 1,831 people (testing cohorts), respectively. In internal and external testing, there was closer agreement between predictions based on measured vs. PCR-calculated ACR than between those based on measured vs. dipstick-calculated ACR. The dipstick-calculated ACR had higher Brier scores than measured ACR from year three for both outcomes, indicating worsening calibration. Models including measured or calculated ACR had similar discrimination: year one-to-five area under the receiver operating characteristic curve of 83-89% for kidney failure and 69-75% for mortality. Thus, if confirmed in different ethnic groups, calculated ACR can be used for risk predictions when the measured ACR is not available. PCR-calculated ACR may have superior performance to dipstick-calculated ACR.

Background: Technique failure is an important outcome measure in research and quality improvement in peritoneal dialysis (PD) programs, but there is a lack of consistency in how it is reported.Methods: We used data collected about incident dialysis patients from 10 Canadian dialysis programs between 1 January 2004 and 31 December 2018. We identified four main steps that are required when calculating the risk of technique failure. We changed one variable at a time, and then all steps, simultaneously, to determine the impact on the observed risk of technique failure at 24 months.Results: A total of 1448 patients received PD. Selecting different cohorts of PD patients changed the observed risk of technique failure at 24 months by 2%. More than one-third of patients who switched to hemodialysis returned to PD—90% returned within 180 days. The use of different time windows of observation for a return to PD resulted in risks of technique failure that differed by 16%. The way in which exit events were handled during the time window impacted the risk of technique failure by 4% and choice of statistical method changed results by 4%. Overall, the observed risk of technique failure at 24 months differed by 20%, simply by applying different approaches to the same data set.Conclusions: The approach to reporting technique failure has an important impact on the observed results. We present a robust and transparent methodology to track technique failure over time and to compare performance between programs.

Empowerment is widely acknowledge as an important source of competitive advantage. However, the effective implementation of employee empowerment efforts continues to pose a serious challenge to many business organizations. Evidence indicates that managers must address seven issues to ensure the success of their empowerment initiatives. These issues are a clear definition of empowerment, the characteristics of empowered employees, the need for empowered workers, the desirability of empowerment, the development of a sense of empowerment, the organizational characteristics that promote employee empowerment, and the role of business leaders in the development of an empowered workforce.

A new kind of intimacy is forming between men and women in the workforce given the entry of more women in traditionally male-dominated professions and the introduction of such management strategies as team building, networking and coalition building. This development may present new challenges for employees who are already confused about what is considered 'proper' male-female behavior and attitudes at work. A study of male and female professionals was conducted to help managers gain insights into the impact of emotionally intimate relationships between the sexes within the organization. The results showed that non-sexual intimate relationships in the workplace are characterized by affection and concern, shared attitudes, and affirmations of each other's worth. It was also found that they are marked by four types of support: emotional, instrumental, informational and appraisal. Sexual involvement was found to lead to resentment, jealousy, gossip and even lawsuits., From the boardroom to the factory floor, men and women now work side by side, forming a new kind of intimacy. A landmark study shows what's happening. In past decades, [...]

The factors that contributed to the production of a flawed mirror for the Hubble Space Telescope lay primarily in a faulty adjustment in the device, and practices of deception and denial among the management of Perkin-Elmer Corp. Ultimately, a larger fault can be found in how the management has changed its principles when the founders died. The project was given a limited budget that made the company's employees resort to cost-shaving, which resulted in the project's failure.

The Competing Values Framework (CVF) is applied to the development of a structured theory in evaluating the efficiency of management information systems (MIS). A concept of MIS effectiveness is developed based on organizational effectiveness through the support of management activity, in order to develop an MIS evaluation theory. The CVF model combinedwith information processing and essential MIS features were used in the development process. The resulting framework is in accordance with MIS experts' views on the characteristics of MIS effectiveness. However, several key internal and external questions need to be addressed in each quadrant of the framework. The completion of an MIS effectiveness theory entails the creation of the two related models that represent the evaluation process and the evaluation context.

The Competing Values Framework is based on a series of studies made on organizational effectiveness. The framework was the result of efforts to further understand the criteria used in evaluating effectiveness. Four separate but interrelated models were identified within the framework, representing a number of unperceived values present in a typical organization. The Internal Process Model reflects an organization's hierarchy where the processes of measurement, documentation and information management are emphasized as vital to achieve stability and control. The Open Systems Model uses adaptability, readiness, growth, resource acquisition and external support as criteria in gauging effectiveness, with an emphasis on innovation and creativity. The Rational Goal Model focuses on maximizing profits through rational action. The Human Relations Model emphasizes the importance of morale and cohesion in human resource management and training.

Amendments to the Florida Condominium Act mandates that a bankruptcy petition filed by the developer and when a state court receiver is not discharged within 30 days of the original appointment are the two new conditions that will trigger a turnover of control of a condominium association. These amendments are examined and explained.

A study has resulted in the formulation of a three-dimensional competing values model for organizational effectiveness. The model illustrates the interaction of the relational, informational, instructional, and transformational forms of presentational communication. The construction of this model using multidimensional scaling involved developing a comprehensive list of descriptors, creating a tool for research on the significance of the relationship between descriptors, and interpreting the responses to the research tool utilizing a computer program that classified the descriptors within the model. Descriptors could be interpreted on the basis of three dimensions. The model suggests alternative approaches in message viewing, the paradoxical nature of presentation effectiveness, an empirical plan for exploring presentations, and a theoretical application.

Background: Guidelines recommend referral for nephrology consultation for people with severe chronic kidney disease (CKD) to improve care and renal outcomes, yet the advocated benefits of nephrology referral on CKD progression in this patient population are unclear. Methods: We linked laboratory and administrative data in Alberta, Canada to identify adults with stage 4 CKD between 2002 and 2014 (follow-up end on March 31, 2017). We studied the association between time-varying receipt of outpatient nephrology consultation and kidney failure (the earlier of renal replacement initiation or eGFR &lt; 10 mL/min/1.73 m2for more than 3 months), accounting for the competing risk of death. Results: Of the 14,382 participants, 41% were ≥ 85 years old, 33% saw a nephrologist as an outpatient, 9% developed kidney failure, and 53% died over a median of 2.6 years. Compared with people who did not see a nephrologist before or at 7 months (median time to consultation), those who did were more likely to develop kidney failure [5-year risk (95% CI) 0.23 (0.21–0.24) vs 0.07 (0.065–0.075)]. With increasing age or higher eGFR, the 5-year risk of kidney failure became progressively smaller, from 0.24 (0.18–0.29) at age &lt; 65 to 0.01 (0.006–0.015) at age ≥ 85 years and from 0.21 (0.18–0.23) at eGFR 15–19 to 0.066 (0.060–0.072) at eGFR 25–29 mL/min/1.73 m2; yet, the hazard ratio of kidney failure (1.6–4.3) increased following nephrology consultation in people who were older or had higher eGFR. Conclusions: Adults with stage 4 CKD who see a nephrologist are more likely to develop kidney failure than those who don’t, especially within lower absolute risk categories. Although selective referral may explain these findings, there is no evidence of an association between nephrology care and reduced risk of kidney failure in people with severe CKD. Studies are needed to assess the benefits of nephrology consultation in people with moderate CKD.

An interview with author and professor Robert E. Quinn and lecturer and entrepreneur Ricardo B. Levy is presented. They talk about the lessons they have learned in leading during economic downturns and organizational financial challenges. They explain how to transform negative feelings like despair, anger and fear into positive ones like clarity, confidence, and hope. They discuss the theoretical principles in organizational downsizing.