Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Pesticide-induced resurgence a hindrance in sustainable forestry: a case study with whitefly Aleurolobus nandiensis and mealybug Planococcus bendovi infesting Gmelina arborea in Tamil Nadu

Gmelina arborea an indigenous tree species valued for its medicinal and timber properties is often attacked by numerous insect defoliators, miners, borers, sap feeders throughout the year including some major pests namely- Calopepla leayana, Tingis beesoni, Prioptera punctipennis, Alcidodes ludificator, Myllocerus sp. etc. As in agriculture the easiest management measure in forestry also comes in the form of different chemical pesticide treatments when the pest population is high and alarming. This investigation is a case study of such pesticide-induced resurgence among secondary insects of G. arborea in nurseries and plantations of Tamil Nadu. Two rare sap feeding insects Planococcus bendovi and Aleurolobus nandiensis in the nursery condition have been exposed directly and indirectly to the different concentrations of chemical pesticide treatment from 2020-2022 repeatedly. Over time the maximum dose of organophosphate pesticide dimethoate 30% EC (Rogor) failed to reach LC50 during insecticide efficacy (EA) testing against P. bendovi bioassay. Similarly, neonicotinoids thiamethoxam 25% WG (Actara) with maximum dose failed in A. nandiensis bioassay. Resurgence index (EHT) showed the higher abundance of A. nandiensis and P. bendovi in treated nursery beds compared to untreated nursery and field conditions by causing the mortality of 10 to 20 % (average) of planting stocks respectively

Studies on Fruit Infestation and Biology of Gall Psyllid Trioza fletcheri Minor Crawford (Triozidae) on Terminalia elliptica Willd. (Combretaceae) in South India

Terminalia elliptica Willd. commonly as called Indian laurel is a deciduous tree of the family Combretaceae and found native to South and South- East Asia.&nbsp; The tree is mainly harvested for the hard wood timber, ethno medicine, tannin extraction and also used as the primary hosts for the production of good quality tasar silk in Central India. The tree is attacked by several insect pests among them leaf gall infestation by the psyllid T. fletcheri cause severe economic loss to tasar silk cultivation. The present study documented the occurrence of gall infestation on the flowers and fruits of T. elliptica by T. fletcheri. The psyllid usually induces galls in leaves and stem of T. elliptica. This is the first report of psyllid T. fletcheri inducing galls on flowers and fruits of T. elliptica. Infestation level in few locations in Western Ghat forest areas of Kerala and Tamil Nadu is assessed. Biology of the gall insect is also studied. The impact of psyllid infestation in the flowers and fruits on the seed production of this important tree species is discussed

Calorie Restriction Modulates Reproductive Development and Energy Balance in Pre-Pubertal Male Rats

The objective was to determine effects of feed restriction and refeeding on reproductive development and energy balance in pre-pubertal male rats. Sprague Dawley rats (n = 32, 24 days old, ~65 g), were randomly allocated into four treatments (n = 8/treatment): (1) Control (CON, ad libitum feed; (2) Mild Restriction (MR, rats fed 75% of CON consumption); (3) Profound Restriction (PR, 50% of CON consumption); or (4) Refeeding (RF, 50% restriction for 14 days, and then ad libitum for 7 days). Feed restriction delayed reproductive development and decreased energy balance and tissue accretion, with degree of reproductive and metabolic dysfunctions related to restriction severity. In RF rats, refeeding largely restored testis weight, sperm production (per gram and total), plasma IGF-1, leptin and insulin concentrations and energy expenditure, although body composition did not completely recover. On Day 50, more CON and RF rats than PR rats were pubertal (5/6, 4/5 and 1/6, respectively; plasma testosterone &gt;1 ng/mL) with the MR group (4/6) not different. Our hypothesis was supported: nutrient restriction of pre-pubertal rats delayed reproductive development, induced negative energy balance and decreased metabolic hormone concentrations (commensurate with restriction), whereas short-term refeeding after profound restriction largely restored reproductive end points and plasma hormone concentrations, but not body composition