A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes.

Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND). We studied 18 obese ND and 16 T2D undergoing three meal tolerance tests (MTT) on three occasions (breakfast, lunch, and dinner). We used plasma glucose, insulin, and FFA concentrations collected at breakfast to test a battery of models and selected the best one based on physiological plausibility, ability to fit the data, precision of parameter estimates, and the Akaike parsimony criterion. The best model assumes that the postprandial suppression of FFA lipolysis is proportional to the above basal insulin, while FFA disposal is proportional to FFA concentration. It was used to compare FFA kinetics in ND and T2D along the day. The maximum lipolysis suppression occurred significantly earlier in ND than T2D (39 ± 6 min vs. 102 ± 13 min, 36 ± 4 min vs. 78 ± 11 min, and 38 ± 6 min vs. 84 ± 13 min, P < 0.01, at breakfast, lunch, and dinner, respectively), making lipolysis significantly lower in ND than T2D. This is mainly attributable to the lower insulin concentration in the second group. This novel FFA model allows to assess lipolysis and insulin antilipolytic effect in postprandial conditions.NEW & NOTEWORTHY In this study, we propose a new mathematical model able to quantify postprandial FFA kinetics and adipose tissue insulin sensitivity in both subjects with obesity without type 2 diabetes (ND) and subjects with type 2 diabetes (T2D). Results show that the slower postprandial suppression of lipolysis in T2D contributes to the higher free fatty acid (FFA) concentration that, in turn, may contribute to hyperglycemia.

Cocaine Augments Dopamine Mediated Inhibition of Neuronal Activity in the Dorsal Bed Nucleus of the Stria Terminalis.

The dorsal region of the bed nucleus of the stria terminalis (dBNST) receives substantial dopaminergic input which overlaps with norepinephrine input implicated in stress responses. Using ex vivo fast scan cyclic voltammetry in male C57BL6 mouse brain slices, we demonstrate that electrically stimulated dBNST catecholamine signals are of substantially lower magnitude and have slower uptake rates compared to caudate signals. Dopamine terminal autoreceptor activation inhibited roughly half of the catecholamine transient, and noradrenergic autoreceptor activation produced an ∼30% inhibition. Dopamine transporter blockade with either cocaine or GBR12909 significantly augmented catecholamine signal duration. We optogenetically targeted dopamine terminals in the dBNST of transgenic (TH:Cre) mice of either sex and, using ex vivo whole-cell electrophysiology, we demonstrate that optically stimulated dopamine release induces slow outward membrane currents and an associated hyperpolarization response in a subset of dBNST neurons. These cellular responses had a similar temporal profile to dopamine release, were significantly reduced by the D2/D3 receptor antagonist raclopride, and were potentiated by cocaine. Using in vivo fiber photometry in male C57BL6 mice during training sessions for cocaine conditioned place preference, we show that acute cocaine administration results in a significant inhibition of calcium transient activity in dBNST neurons compared to saline administration. These data provide evidence for a mechanism of dopamine-mediated cellular inhibition in the dBNST and demonstrate that cocaine augments this inhibition while also decreasing net activity in the dBNST in a drug reinforcement paradigm.SIGNIFICANCE STATEMENTThe dorsal bed nucleus of the stria terminalis (dBNST) is a region highly implicated in mediating stress responses, however, the dBNST also receives dopaminergic inputs from classically defined drug reward pathways. Here we used various techniques to demonstrate that dopamine signaling within the dorsal BNST region has inhibitory effects on population activity. We show that cocaine, an abused psychostimulant, augments both catecholamine release and dopamine-mediated cellular inhibition in this region. We also demonstrate that cocaine administration reduces population activity in the dBNST, in vivo Together these data support a mechanism of dopamine-mediated inhibition within the dBNST, providing a means by which drug-induced elevations in dopamine signaling may inhibit dBNST activity to promote drug reward.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

Taxonomic Interference Associated with Phonemic Paraphasias in Agrammatic Primary Progressive Aphasia.

Phonemic paraphasias are thought to reflect phonological (post-semantic) deficits in language production. Here we present evidence that phonemic paraphasias in non-semantic primary progressive aphasia (PPA) may be associated with taxonomic interference. Agrammatic and logopenic PPA patients and control participants performed a word-to-picture visual search task where they matched a stimulus noun to 1 of 16 object pictures as their eye movements were recorded. Participants were subsequently asked to name the same items. We measured taxonomic interference (ratio of time spent viewing related vs. unrelated foils) during the search task for each item. Target items that elicited a phonemic paraphasia during object naming elicited increased taxonomic interference during the search task in agrammatic but not logopenic PPA patients. These results could reflect either very subtle sub-clinical semantic distortions of word representations or partial degradation of specific phonological word forms in agrammatic PPA during both word-to-picture matching (input stage) and picture naming (output stage). The mechanism for phonemic paraphasias in logopenic patients seems to be different and to be operative at the pre-articulatory stage of phonological retrieval. Glucose metabolic imaging suggests that degeneration in the left posterior frontal lobe and left temporo-parietal junction, respectively, might underlie these different patterns of phonemic paraphasia.

Young-onset diabetes, nutritional therapy and novel insulin delivery systems: a report from the 21st Hong Kong Diabetes and Cardiovascular Risk Factors - East Meets West Symposium.

The prevalence and incidence of young-onset diabetes are increasing in many parts of the world, with the most rapid increase occurring in Asia, where one in five people with diabetes are diagnosed below the age of 40 years. Accumulation of glycaemic burden from an early age significantly increases the lifetime risks of developing complications from diabetes. Despite impending health threats, young people fare worse in the control of blood glucose and other metabolic risk factors. Challenges in the management of young-onset diabetes are compounded by heterogeneity of the underlying causes, pathophysiology and clinical phenotypes in this group. Effective characterization of people with diabetes has implications in steering the choice of glucose-lowering drugs, which, in turn, determines the clinical outcome. Medical nutritional therapy is key to effective management of people with diabetes but dietary adherence is often suboptimal among younger individuals. A recently published consensus report on nutritional therapy addresses dietary management in people with prediabetes as well as diabetes, and summarizes clinical evidence regarding macronutrient and micronutrient composition as well as eating patterns in people with diabetes. For people with type 1 diabetes, automated insulin delivery systems have rapidly evolved since the concept was first introduced at the National Institute of Health and the Juvenile Diabetes Research Foundation in 2005. The subsequent development of a type 1 diabetes simulator, developed using detailed human physiology data on carbohydrate metabolism replaced the need for pre-clinical animal studies and facilitated the seamless progression to artificial pancreas human clinical trials.

Identification and characterization of novel transglycosylating α-glucosidase from Aspergillus neoniger.

AIM: Aspergillus niger is well established for secreting α-glucosidase having transglycosylation activity, which is used as processing aid for synthesis of isomaltooligosaccharides. The present study focuses on identification and characterization of a non-niger Aspergillus isolate and its gene conferring strong transglycosylation activity. METHODS AND RESULTS: The soil isolate was identified as Aspergillus neoniger belonging to Aspergillus section Nigri using ITS (internal transcribed spacer) and ß-tubulin analysis. The sequence analysis of gene responsible for α-glucosidase synthesis revealed significant nucleotide variations when compared to other Aspergillus species. Molecular docking studies using the homology model revealed the presence of threonine at 694 subsite position instead of asparagine as in case of A. niger's α-glucosidase. The enzyme was purified to several fold using DEAE Sepharose-CL6B column and on SDS-PAGE analysis, it was found to be 145 kDa. MS/MS analysis of the purified enzyme validated the presence of threonine at 694 position. Commercial α-glucosidase (Transglucosidase L 'Amano') derived from A. niger and the α-glucosidase from isolate were compared for transglycosylation activity using constant test conditions. α-glucosidase from the isolate produced 27·4% higher panose when compared to that of commercial enzyme. Moreover, the rate of secondary hydrolysis of panose is much lower in case of the isolate's enzyme. CONCLUSIONS: Fungal isolate A. neoniger was characterized, and its gene conferring α-glucosidase activity was established for strong transglycosylation activity having higher panose yields. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report to establish a variant of α-glucosidase having strong transglycosylation activity from A. neoniger strain. We have demonstrated that this enzyme when used as processing aid could improve panose significantly, which is a potential prebiotic. Also, the sequence analysis established in our studies could provide pointers for directed evolution of this enzyme to further improve transglycosylation activity.

Beyond HbA1c : using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision-making.

Assessment of glycaemic outcomes in the management of Type 1 and Type 2 diabetes has been revolutionized in the past decade with the increasing availability of accurate, user-friendly continuous glucose monitoring (CGM). This advancement has brought a need for new techniques to appropriately analyse and understand the voluminous and complex CGM data for application in research-related goals and clinical guidance for individuals. Traditionally, HbA1c was established using the Diabetes Control and Complications Trial (DCCT) and other trials as the ultimate measure of glycaemic control in terms of efficacy and, by default, risk of microvascular complications of diabetes. However, it is acknowledged that HbA1c alone is inadequate at describing an individual's daily glycaemic variation and risks for hypo- and hyperglycaemia, and it does not provide the guidance needed to decrease those risks. CGM data provide means by which to characterize an individual's daily glycaemic excursions on a different time scale measured in minutes rather than months. As a consequence, clinical reports, such as the ambulatory glucose profile, increasingly include summary statistics related to averages (mean glucose, time in range) as well as markers related to glycaemic variability (coefficient of variation, standard deviation). However, there is a need to translate those metrics into specific risks that can be addressed in an actionable plan by individuals with diabetes and providers. This review presents several clinical scenarios of glycaemic outcomes from CGM data that can be analysed to describe glycaemic variability and its attendant risks of hyperglycaemia and hypoglycaemia, moving towards relevant interpretation of the complex CGM data streams.

Consensus on the Management of Posterior Urethral Valves from Antenatal Period to Puberty.

The need for successful management of posterior urethral valves always captivates the minds of pediatric surgeons. Its success, however, depends on several factors ranging from prenatal preservation of upper tracts to postoperative pharmacological compliance. Regardless of measures available, some cases do not respond and progress to end stage. The management depends on several issues ranging from age and severity at presentation to long-term follow-up and prevention of secondary renal damage and managing valve bladder syndrome. This article is based on a consensus to the set of questionnaires, prepared by research section of Indian Association of Paediatric Surgeons and discussed by experienced pediatric surgeons based in different institutions in the country. Standard operating procedures for conducting a voiding cystourethrogram and cystoscopy were formulated. Age-wise contrast dosage was calculated for ready reference. Current evidence from literature was also reviewed and included to complete the topic.

Distinguishing postpartum and antepartum depressive trajectories in a large population-based cohort: the impact of exposure to adversity and offspring gender.

BACKGROUND: Distinguishing temporal patterns of depressive symptoms during pregnancy and after childbirth has important clinical implications for diagnosis, treatment, and maternal and child outcomes. The primary aim of the present study was to distinguish patterns of chronically elevated levels of depressive symptoms v. trajectories that are either elevated during pregnancy but then remit after childbirth, v. patterns that increase after childbirth. METHODS: The report uses latent growth mixture modeling in a large, population-based cohort (N = 12 121) to investigate temporal patterns of depressive symptoms. We examined theoretically relevant sociodemographic factors, exposure to adversity, and offspring gender as predictors. RESULTS: Four distinct trajectories emerged, including resilient (74.3%), improving (9.2%), emergent (4.0%), and chronic (11.5%). Lower maternal and paternal education distinguished chronic from resilient depressive trajectories, whereas higher maternal and partner education, and female offspring gender, distinguished the emergent trajectory from the chronic trajectory. Younger maternal age distinguished the improving group from the resilient group. Exposure to medical, interpersonal, financial, and housing adversity predicted membership in the chronic, emergent, and improving trajectories compared with the resilient trajectory. Finally, exposure to medical, interpersonal, and financial adversity was associated with the chronic v. improving group, and inversely related to the emergent class relative to the improving group. CONCLUSIONS: There are distinct temporal patterns of depressive symptoms during pregnancy, after childbirth, and beyond. Most women show stable low levels of depressive symptoms, while emergent and chronic depression patterns are separable with distinct correlates, most notably maternal age, education levels, adversity exposure, and child gender.

Understanding frames: A UK survey of parents and professionals regarding the use of standing frames for children with cerebral palsy.

BACKGROUND: Standing frames are used for children with cerebral palsy (CP). They may improve body structure and function (e.g., reducing risk of hip subluxation, and improving bladder and bowel function), improving activity (e.g., motor abilities) and participation (e.g., interaction with peers), but there is little evidence that they do. We aimed to identify current UK standing frame practice for children with CP and to understand stakeholder views regarding their clinical benefits and challenges to use. METHOD: Three populations were sampled: clinicians prescribing standing frames for children with CP (n = 305), professionals (health and education) working with children with CP who use standing frames (n = 155), and parents of children with CP who have used standing frames (n = 91). Questionnaires were developed by the co-applicant group and piloted with other professionals and parents of children with CP. They were distributed online via clinical and parent networks across the UK. RESULTS: Prescribing practice was consistent, but achieving the prescribed use was not always possible. Respondents in all groups reported the perceived benefits of frames, which include many domains of the International Classification of Functioning Disability and Health for Children and Youth. Challenges of use are related to physical space and child-reported pain. CONCLUSIONS: These survey findings provide information from key stakeholders regarding current UK standing frame practice.

Understanding frames: A qualitative study of young people's experiences of using standing frames as part of postural management for cerebral palsy.

BACKGROUND: Consensus opinion supports standing frame use as part of postural management for nonambulant young people with cerebral palsy. Although the rationale for standing frame use and the associated challenges have been described, little attention has been given to the users' experiences. The aim of the current study was to explore young people's positive and negative experiences, and attitudes regarding standing frame use. METHODS: Framework analysis informed an open exploration of young people's opinions of standing frames. Using semistructured interviews, 12 young people with cerebral palsy (6 female) were interviewed, providing the data set for transcription and thematic analysis. FINDINGS: The first theme "attitudes to standing frames" describes the young people's understanding of why they use standing frames. Although standing frames can be painful, some young people believe they should be endured to improve their body structure and function. There were mixed views about the impact standing frames have socially, with some young people feeling excluded from their peers, and others feeling as though standing frames helped them "fit in." Some young people are not offered a choice about how and when they use their standing frame. The second theme "challenges of standing frame use" highlights the issues with standing frame use such as manual handling, interference from siblings, and the lack of aesthetically pleasing standing frame designs. CONCLUSIONS: Young people report benefits related to choice, pain relief, and participation but can also cause pain, discomfort, and reduced independence and participation. Healthcare professionals should have open, informative conversations about potential benefits and challenges of standing frames on all aspects of the young people's lives, including participation and activity.

Enhancement of toxic Cr (VI), Fe, and other heavy metals phytoremediation by the synergistic combination of native Bacillus cereus strain and Vetiveria zizanioides L.

Bioremediation of Cr (VI), Fe, and other heavy metals (HMs) through plant-microbes interaction is one of the efficient strategies due to its high efficiency, low cost, and ecofriendly nature. The aim of the study was to isolate, characterize, and assess the potential of rhizospheric bacteria to enhance growth and metal accumulation by the chromium hyperaccumulator Vetiveria zizanoides. The bacterial strain isolated from mine tailings was identified to be Bacillus cereus (T1B3) strain exhibited plant growth-promoting traits including, 1-aminocyclopropane-1-carboxylate deaminase, indole acetic acid, and siderophores production, nitrogen fixation, and P solubilization. Removal capacity (mg L-1) of T1B3 strain was 82% for Cr+6 (100), 92% for Fe (100), 67% for Mn(50), 36% for Zn (50), 31% for Cd (30), 25% for Cu (30), and 43% for Ni (50) during the active growth cycle in HM-amended, extract medium. Results indicate that inoculating the native V. zizanioides with T1B3 strain improves its phytoremediation efficiency of HMs. The mineralogical characteristics of chromite ore tailings and soil were also confirmed by X-ray diffraction, Fourier Transform Infrared, scanning electron microscope-energy dispersive spectroscopy analysis.

Parental optimism about childhood obesity-related disease risks.

OBJECTIVES: Most parents believe childhood obesity is a problem for society, but not for their own children. We sought to understand whether parents' risk assessment was skewed by optimism, the tendency to overestimate one's chances of experiencing positive events. METHODS: We administered a national web-based survey to 502 parents of 5-12-year-old children. Parents reported the chances that (a) their child and (b) 'a typical child in their community' would be overweight or obese, and develop hypertension, heart disease, type 2 diabetes and depression in adulthood. Respondents self-reported demographic and health information, and we obtained demographic and health information about the typical child using zip code-level census and lifestyle data. We used regression models with fixed effects to evaluate whether optimism bias was present in parent predictions of children's future health outcomes. RESULTS: Parents had 40 times lower adjusted odds (OR=0.025, P<0.001, 99% CI: 0.006, 0.100) of predicting that their child (versus a typical child) would be overweight or obese in adulthood. Of the 20% of parents who predicted their child would be overweight in adulthood, 93% predicted the typical child would also be overweight in adulthood. Controlling for health and demographic characteristics, parents estimated that their children's chances of developing obesity-related comorbidities would be 12-14 percentage points lower those that of a typical child. CONCLUSIONS: Parent risk assessment is skewed by optimism, among other characteristics. More accurate risk perception could motivate parents to engage in behavior change.

A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism.

Mutations in STXBP1 have recently been identified as a cause of infantile epileptic encephalopathy. The underlying mechanism of the disorder remains unclear and, recently, several case reports have described broad and progressive neurological phenotypes in addition to early-onset epilepsy. Herein, we describe a patient with early-onset epilepsy who subsequently developed a progressive neurological phenotype including parkinsonism in her early teens. A de novo mutation in STXBP1 (c.416C>T, p.(Pro139Leu)) was detected with exome sequencing together with profound impairment of complex I of the mitochondrial respiratory chain on muscle biopsy. These findings implicate a secondary impairment of mitochondrial function in the progressive nature of the disease phenotype.

Malsoor virus, a novel bat phlebovirus, is closely related to severe fever with thrombocytopenia syndrome virus and heartland virus.

During a survey in the year 2010, a novel phlebovirus was isolated from the Rousettus leschenaultii species of bats in western India. The virus was identified by electron microscopy from infected Vero E6 cells. Phylogenic analysis of the complete genome showed its close relation to severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses, which makes it imperative to further study its natural ecology and potential as a novel emerging zoonotic virus.

Serum lipoprotein ratios as markers of insulin resistance: a study among non-diabetic acute coronary syndrome patients with impaired fasting glucose.

BACKGROUND & OBJECTIVES: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. METHODS: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used for insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC) of the receiver operating characteristic (ROC) curves were used to compare the power of these serum lipoprotein ratios as markers. RESULTS: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. INTERPRETATION & CONCLUSIONS: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

Assessment of insulin action on carbohydrate metabolism: physiological and non-physiological methods.

Carbohydrate metabolism in humans is regulated by insulin secretion from pancreatic ß-cells and glucose disposal by insulin-sensitive tissues. Insulin facilitates glucose utilization in peripheral tissues and suppresses hepatic glucose production. Any defects in insulin action predispose an individual to glucose intolerance and Type 2 diabetes mellitus. Early detection of defects in insulin action could provide opportunities to prevent or delay progression of the disease state. There are different approaches to assess insulin action. Initial methods, such as peripheral insulin concentration and simple indices, have several limitations. Subsequently, researchers developed methodologies using intravenous glucose infusion to determine glucose fluxes. However, these methodologies are limited by being non-physiological. Newer, innovative techniques that have been developed are more sophisticated and physiological. By modelling glucose kinetics using isotope dilution techniques, several robust parameters can be obtained that are physiologically relevant and sound. This brief review summarizes most of the non-physiological and physiological methodologies used to measure the variables of insulin action.

Cancer risk with alemtuzumab following kidney transplantation.

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.