Urinary biomarkers for the prediction of diabetic nephropathy, cardiovascular disease and mortality in individuals with type 1 diabetes

Introduction: Diabetic nephropathy (DN) is a devastating diabetes complication. DN is associated with a competitive risk of either progression to a worse stage of DN or premature mortality. Mortality is mainly due to cardiovascular events. Tubular dysfunction is involved in the loss of kidney function. Therefore, tubular biomarkers could add significant benefit to early identification of DN, prediction of DN progression and to screening for risk of cardiovascular events. Aims: The aims of this thesis were to investigate, in individuals with T1DM, if three urinary biomarkers [liver-type fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1) and urinary adiponectin (ADP)] could outperform the currently available biomarkers for the prediction of DN development and progression or even be causally related to the loss of kidney function. In addition, the thesis aimed to investigate if these biomarkers could predict cardiovascular disease (CVD) and premature mortality. Subjects and methods: All individuals with T1DM included in this thesis were enrolled between January 1998 and December 2002. The studies were part of the Finnish Diabetic Nephropathy Study (FinnDiane), a nationwide cohort of individuals with T1DM followed prospectively at more than 80 centres throughout Finland. The participants were followed for a median of 5.8 to 14.1 years, and clinical outcomes were prospectively evaluated. Results: In study I, L-FABP was shown to be an independent predictor of progression of DN irrespective of the disease stage and did not improve the risk prediction of DN progression. In study II, urinary ADP was an independent predictor of progression to end-stage renal disease (ESRD) and performed even better than AER and as good as eGFR. In study III, KIM-1 did not predict the progression to ESRD independently of AER. However, the Mendelian randomization (MR) analysis showed that KIM-1 is very likely to play a causal role in the loss of eGFR. In study IV, L-FABP was an independent predictor of stroke and premature mortality but did not add any predictive benefit on top of AER and eGFR. It is of note that urinary ADP and AER were common determinants of all tested biomarkers. Discussion and conclusions: By predicting the progression of DN, these biomarkers proved that tubular dysfunction is an important part of DN progression. However, judging by their baseline determinants, the studied tubular biomarkers represent much more than tubular injury, capturing also glomerular damage as well as systemic factors. L-FABP was an as good predictor as eGFR or AER of stroke or premature mortality, while the other biomarkers predicted various other cardiovascular outcomes. A causal relationship between these biomarkers and loss of kidney function could be demonstrated only for KIM-1, but this particular observation confirms a causal role of tubular dysfunction for the DN progression.Inledning: Diabetisk nefropati (DN) är en förödande diabeteskomplikation. DN är förknippad med en konkurrensrisk för antingen progression till ett sämre stadium av DN eller för tidig dödlighet. Dödlighet beror främst på kardiovaskulära händelser. Tubular dysfunktion är involverad i förlusten av njurfunktionen. Därför kan tubulära biomarkörer ge betydande fördelar vid tidig identifiering av DN, förutsägelse av DN-progression och screening för risk för kardiovaskulära händelser. Syfte: Syftet med denna avhandling var att undersöka, hos personer med typ 1-diabetes (T1DM), om tre urinbiomarkörer [liver-type fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), och urin adiponectin (ADP)] kunde överträffa de biomarkörer som för närvarande finns tillgängliga för förutsägelse av DN-utveckling och progression eller till och med vara kausalt relaterade till förlusten av njurfunktionen. Dessutom syftade avhandlingen till att undersöka om dessa biomarkörer kunde förutsäga hjärt-kärlsjukdom (CVD) och för tidig dödlighet. Ämnen och metoder: Alla individer med T1DM som ingår i denna avhandling registrerades mellan januari 1998 och december 2002. Studierna var en del av den finska diabetiska nefropati-studien (FinnDiane), en rikstäckande grupp av individer med T1DM som följs prospektivt på mer än 80 centra genom Finland. Deltagarna följdes i en median på 5,8 till 14,1 år och kliniska resultat utvärderades prospektivt. Resultat: I studie I visades L-FABP vara en oberoende prediktor för progression av DN oberoende av sjukdomsstadiet och förbättrade inte riskprognosen för DN-progression. I studie II var urin ADP en oberoende prediktor för progression till slutstadiet njursjukdom (ESRD) och presterade ännu bättre än AER och lika bra som eGFR. I studie III förutsade inte KIM-1 utvecklingen till ESRD oberoende av AER. Men den mendeliska randomiseringsanalysen (MR) visade att KIM-1 mycket sannolikt kommer att spela en kausal roll i förlusten av eGFR. I studie IV var L-FABP en oberoende prediktor för stroke och för tidig dödlighet men tillförde ingen prediktiv fördel utöver AER och eGFR. Det noteras att urin ADP och AER var vanliga faktorer för alla testade biomarkörer. Diskussion och slutsatser: Genom att förutsäga utvecklingen av DN visade dessa biomarkörer att tubulär dysfunktion är en viktig del av DN-progressionen. Att döma av deras baslinjeavgörande faktorer representerar de studerade tubulära biomarkörerna dock mycket mer än tubulär skada, och fångar också glomerulär skada såväl som systemfaktorer. L-FABP var en lika bra prediktor som eGFR eller AER för stroke eller för tidig dödlighet, medan de andra biomarkörerna förutspådde olika andra kardiovaskulära resultat. Ett orsakssamband mellan dessa biomarkörer och förlust av njurfunktion kunde endast påvisas för KIM-1, men denna speciella observation bekräftar en orsaksroll av tubulär dysfunktion för DN-progression

Romania: Subsistence Farming After Imposed Industrialisation

During the transition to the market economy, real earnings fell sharply. The existence of an underground economy generally deemed to have grown at a worryingly fast rate has had a strong effect on the (rising) level and distribution of income (increase in inequalities). The Communist regimes extensive housing estate building programme, mainly in the urban areas, gave virtually all Romanian citizens housing. These State-owned dwellings were sold to their tenants after 1989, such that 95% of households now own their own housing. However, the downturn in construction in the 1990s prompted a housing crisis. Housing conditions remain poor particularly in the rural areas. The frequency of poverty is particularly high in rural areas where a large proportion of households have low earnings, and sub-standard dwellings. A high percentage of urban households also have to deal with the pressure of growing financial difficulties due to unemployment and low pension payments.Multiple Dimensions of Poverty, Socialist Country in Transition, Romania

Birth weight and atopic dermatitis: systematic review and meta-analysis

Several studies examined the relationship between birth weight and atopic diseases, but no consensus has yet been reached regarding the results.The purpose of this paper was to perform a meta-analysis of the existing studies regarding the role of birth weight in the occurrence of atopic dermatitis. We carried out an extensive search in the international databases (Pubmed, Cochrane Library, and Web of Knowledge). We selected the cross-sectional, case-control, and cohort studies which analyzed the role of birth weight in the occurrence of atopic dermatitis. We performed a meta-analysis of the selected studies, and calculated the odds ratio (OR) and corresponding 95% confidence intervals (95% CI). We included 10 studies in the final meta-analysis, which comprised 110974 patients. Weight classification was in compliance with Pediatric Nutrition Surveillance System (PedNSS) Health Indicators. In the first meta-analysis, we selected patients with low weight (below 2500 g) and atopic dermatitis and compared them with those with normal weight (2500 – 4000 g) and atopic dermatitis. The analysis showed that low birth weight represents a protective factor in the occurrence of atopic dermatitis (OR = 0.68, CI: 0.63 – 0.75, P&lt;0.0001). In the second meta-analysis, we compared patients with high weight (over 4000 g) and atopic dermatitis with those with normal weight and atopic dermatitis. The results indicated that increased birth weight represents a risk factor for atopic dermatitis (OR = 1.1; CI: 1.02 – 1.17; P = 0.01)Thus, low birth weight represents a protective factor for the occurrence of atopic dermatitis and high birth weight represents a risk factor for the occurrence of this disease.</p

Performance analysis of symbol timing estimators for time-varying MIMO channels

The purpose of this thesis is to derive and analyze the theoretical limits for estimatingthe symboltiming delayof Multiple-Input Multiple-Output (MIMO)systems. Two main N X M system models are considered, where N represents the number of transmit antennas and M denotes the number of receive antennas, the 2 X 2 system used by S.-A. Yangand J. Wu and the 4 X 4system used by Y.-C. Wu and E. Serpedin. The second model has been extended to take into account the symbol time-varying fading. The theoretical estimation limits are shown by several bounds: modified Cramer-Rao bound (MCRB), Cramer-Rao bound (CRB) and Barankin bound (BB). BB will be exploited to obtain accurate information regarding the necessary length of data to obtain good estimation. Two scenarios for synchronization are presented: data-aided (DA) and non-data-aided (NDA). Two models for the fading process are considered: block fading and symbol time-varying fading, respectively, the second case being assumed to be Rayleigh distributed. The asymptotic Cramer-Rao bounds for low signal-to-noise ratio (low-SNR) and for high-SNR are derived and the performance of several estimators is presented. The performance variation of bounds and estimators is studied byvarying different parameters, such as the number of antennas, the length of data taken into consideration during the estimation process, the SNR, the oversampling factor, the power and the Doppler frequency shift of the fading

Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature

<p>Abstract</p> <p>Background</p> <p>Delay in diagnosis of pulmonary tuberculosis results in increasing severity, mortality and transmission. Various investigators have reported about delays in diagnosis of tuberculosis. We aimed at summarizing the data on these delays in diagnosis of tuberculosis.</p> <p>Methods</p> <p>A systematic review of literature was carried out. Literature search was done in Medline and EMBASE from 1990 to 2008. We used the following search terms: delay, tuberculosis, diagnosis, and help-seeking/health-seeking behavior without language restrictions. In addition, indices of four major tuberculosis journals were hand-searched. Subject experts in tuberculosis and authors of primary studies were contacted. Reference lists, review articles and text book chapters were also searched. All the studies were assessed for methodological quality. Only studies carried out on smear/culture-positive tuberculosis patients and reporting about total, patient and health-care system delays were included.</p> <p>Results</p> <p>A total of 419 potential studies were identified by the search. Fifty two studies qualified for the review. The reported ranges of average (median or mean) total delay, patient delay, health system delay were 25–185 days, 4.9–162 days and 2–87 days respectively for both low and high income countries. Average patient delay was similar to health system delay (28.7 versus 25 days). Both patient delay and health system delay in low income countries (31.7 days and 28.5 days) were similar to those reported in high income countries (25.8 days and 21.5 days).</p> <p>Conclusion</p> <p>The results of this review suggest that there is a need for revising case-finding strategies. The reported high treatment success rate of directly observed treatment may be supplemented by measures to shorten the delay in diagnosis. This may result in reduction of infectious cases and better tuberculosis control.</p

Illumination of a production facility for communication and electric power cables

Sight represents 90% of our sensory everyday life. In specific work conditions, like long distance communication and electric power cable production, sight is by far more important. Work personnel must distinguish between many colours cables in verifying the cable delivered finally after the machine assembling. Errors are very costly since any non-conformity results in an entire production stock rejection. The luminosity in the production facility is estimated by similitude of different room scales and the necessary of artificial illumination. The results will be computed per the level of illumination indicated for production. A scaled-up estimation will be for the production facility, and is corrected with respect to the production equipment situated between the center of the room, occupied by the directing staff, and the facility edges. Equipment and machines are placed in a visible way from the central area occupied by offices. Results are analysed to improve facility design in terms of rectangularity ratio, colour of the walls, ceiling and floor and light sources emplacement

Who Is More Rational During a Crisis Situation: Men Who Do Not Spend Their Money or Women Who Think About the Future?

The COVID-19 pandemic was one of the most important events in entire world history. This event changed and influenced human lives forever. The changes in human behavior were so relevant when the pandemic started. Furthermore, due to the recorded data and our personal experiences, research on this subject can serve as an instrument to reduce and minimize the impact of future health crises. We need to analyze, study, and draw significant conclusions to understand as much as possible how consumers reacted in order to avoid such situations in the future. In this article, I analyze data obtained from a survey about the consumer behavior of agro-food products during the COVID-19 crisis. Specifically, I study the influence of gender on the financial resource allocation of consumers of agro-food products during the lockdown period of March to June 2020. This analysis was performed using linear regression with binary variables. We can develop plans and safety measures based on the results and conclusions of the article. We also can use the article results and conclusion to have an image of consumer behavior toward agro-food products during health crises, to know how we can action. On the other hand, the analysis can be very helpful for retailers of agro-food products. They can develop new marketing or sales strategies based on the findings to maximize their income. These new strategies can be utilized during health crises, maximizing the opportunity presented

Considerations on glycaemic control in older and/or frail individuals with diabetes and advanced kidney disease

The increasing prevalence of chronic kidney disease (CKD) and diabetes over the last decade has resulted in increasing numbers of frail older patients with a combination of these conditions. Current treatment guidelines may not necessarily be relevant for such patients, who are mostly excluded from the trials upon which these recommendations are based. There is a paucity of data upon which to base the management of older patients with CKD. Nearly all current guidelines recommend less-tight glycaemic control for the older population, citing the lack of proven medium-term benefits and concerns about the high short-term risk of hypoglycaemia. However, reports from large landmark trials have shown potential benefits for both microvascular and macrovascular complications, though the relevance of these findings to this specific population is uncertain. The trials have also highlighted potential alternative explanations for the hazards of intensive glycaemic control. These include depression, low endogenous insulin reserve, low body mass index and side effects of the medication. Over the last few years, newer classes of hypoglycaemic drugs with a lower risk of hypoglycaemia have emerged. This article aims to present a balanced view of advantages and disadvantages of intense glycaemic control in this group of patients, which we hope will help the clinician and patient to come to an individualized management approach.Peer reviewe