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The development and introduction of modulator therapies have completely shifted the paradigm for the treatment of cystic fibrosis (CF). Highly effective modulator therapies have driven marked improvements in lung function, exacerbation rate, weight and quality of life in CF patients. However, their effect on CF related diabetes (CFRD) is not well delineated. The role of CF transmembrane conductance regulator (CFTR) in CFRD pathogenesis is inadequately understood and research aimed at deciphering the underlying mechanisms of CFRD continues to evolve. In this review, we summarize what is known regarding the effect of CFTR modulators on CFRD. Small studies using ivacaftor monotherapy in gating mutations have revealed improvement in insulin secretion, glucose tolerance and/or decrease in insulin requirement. However, lumacaftor/ivacaftor studies (primarily in delta F 508 homozygous) have not revealed significant improvement in CFRD or glucose tolerance. No studies are yet available regarding the effect of the highly effective triple therapy (elexacaftor/tezacaftor/ivacaftor) on CFRD or insulin secretion. CFTR modulators might affect development or progression of CFRD through many mechanisms including improving insulin secretion by correcting the CFTR defect directly, improving ductal function, reducing islet inflammation, and improving incretin secretion or by enhancing insulin sensitivity via reduced systemic inflammation and increased physical activity driven by improved lung function and quality of life. On the other hand, they can stimulate appetite and improve gastrointestinal function resulting in increased caloric intake and absorption, driving excessive weight gain and potentially increased insulin resistance. If the defect in insulin secretion is reversible then it is possible that initiation of CFTR modulators at a younger age might help prevent CFRD. Despite the advances in CF management, CFRD remains a challenge and knowledge continues to evolve. Future studies will drive better understanding of the role of highly effective CFTR modulators in CFRD.

We report the analysis of the young star clusters NGC 1960, NGC 2453 and NGC 2384 observed in the J (1.12 µm), H (1.65 µm) and K (2.2 µm) bands. Estimates of reddening, distance and age as E(B − V ) = 0.25, d = 1380 pc and t = 31.6 to 125 Myr for NGC 1960, E(B − V ) = 0.47, d = 3311 pc and t = 40 to 200 Myr for NGC 2453 and E(B −V ) = 0.25, d = 3162 pc and t = 55 to 125 Myr for NGC 2384 have been obtained. Also, we have extended the color-magnitude diagrams of these clusters to the fainter end and thus extended the luminosity functions to fainter magnitudes. The evolution of the main sequence and luminosity functions of these clusters have been compared with themselves as well as Lyngå 2 and NGC 1582.

In this paper, using 2MASS photometry, we study the mass functions $\phi(M) = dN/dM \propto M^{-\alpha}$ of a sample of nine clusters of ages varying from 4 Myr--1.2 Gyr and Galactocentric distances from 6--12 kpc. We look for evidence of mass segregation in these clusters by tracing the variation in the value of $\alpha$ in different regions of the cluster as a function of the parameter $\tau = t_{age}/t_{relax}$ (where $t_{age}$ is the age of the cluster and $t_{relax}$ is the relaxation time of the cluster), Galactocentric distance, age and size of the cluster. The value of $\alpha$ value increases with age and $\tau$ and fits straight lines with slopes $m$ and y-intercepts $c$ given by $m=0.40\pm0.03$, $c=-1.86\pm0.27$ and $m=0.01\pm0.001$, $c=-0.85\pm0.02$, respectively and is a clear indicator of the dynamical processes involved. The confidence level of the Pearson's product-moment correlation of $\alpha$ with age is 0.76 with p=0.002 and with $\tau$ is 0.71 with p=0.007. The value of $\alpha$ also increases with Galactocentric distance, indicating the presence of a larger relative number of low mass stars in clusters at larger Galactocentric distances. We find two clusters, viz. IC 1805 and NGC 1893, with evidence of primordial or early dynamical mass segregation. Implications of primordial mass segregation on the formation of massive stars and recent results supporting early dynamical mass segregation are discussed.Comment: Accepted MNRAS, 28 page

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