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Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population.

APG777 is a high-affinity, half-life extended, humanized anti-IL-13 IgG1 monoclonal antibody (mAb) that blocks formation of the IL-13/IL-13Rα1/IL-4Rα complex. Results of the first study of APG777 in humans, including safety, PK, and PD, are reported through 6 months.

Byline: Reghu. Sukumaran Nair, Binitha. Rajeswari, Priyakumari. Thankamony, Kusumakumary. Parukuttyamma We report two cases of mucoepidermoid carcinoma occurring as a second neoplasm following treatment for acute lymphoblastic leukemia. Both patients [...]

Though survival in bilateral retinoblastoma (RB) has improved due to advancement in diagnostics and treatment modalities, children require long-term follow-ups for recurrence and second malignancies. We report a case of bilateral RB in a 7-month-old baby who was treated with chemotherapy, transpupillary thermotherapy, and periocular carboplatin for both eyes following which there was complete regression of tumour. Six and a half years after treatment, the child presented with metastatic recurrence of tumour in the left ulna. He was treated successfully with chemotherapy, extracorporeal radiation and reimplantation therapy. A less aggressive treatment approach for isolated bone relapse may be considered in selected cases.

Primary mediastinal (thymic) large B-cell lymphoma is an aggressive B-cell lymphoma. It comprises <3% of all pediatric non-Hodgkin lymphomas (NHLs). Primary mediastinal (thymic) large B-cell lymphoma usually presents with serous pleural effusion, but presentation with chylous pleural and pericardial effusions is rare. We present a child who presented with features of a superior mediastinal syndrome. Biopsy of the mediastinal mass confirmed the diagnosis of large B-cell lymphoma. In view of nonimprovement of respiratory distress with chemotherapy and persistence of features of superior mediastinal syndrome, the child was evaluated and found to have massive pleural and pericardial effusion on imaging. Therapeutic thoracentesis and pericardiocentesis revealed chylous nature of the fluid.

The present study describes a 7-year-old male child who had attended the Pediatric Oncology Clinic of the Regional Cancer Centre, Thiruvananthapuram, Kerala, India, and was pathologically confirmed to have B-Acute Lymphoblastic Leukemia (B-ALL). Conventional cytogenetics analysis at diagnosis showed the presence of a double Philadelphia chromosome and the karyotype of the case was 47, XY, t(9;22)(q34;q11.2), + der(22)t(9;22). FISH, done as a molecular confirmation of the translocation, t(9;22)(q34;q11.2), and this case showed an additional fusion signal that confirms the presence of double Ph. As far as we are aware, this represents the initial and only  occurrence of an abnormality report regarding the double Philadelphia chromosome in pediatric B-ALL within India. The double Philadelphia chromosome in B-ALL has a very poor prognosis despite aggressive treatment with chemotherapy. This study reveals the importance of conventional and molecular cytogenetic analysis in risk stratification and prognosis prediction of pediatric B-ALL. The risk stratification based on the conventional and molecular cytogenetic analysis may be taken into consideration for deciding the treatment strategy for each patient.

Infections in acute liver failure (ALF) increase the associated morbidity and mortality, and often hamper the possibility of transplantation. Two-thirds of the infections in ALF are bacterial while one-third is fungal. High suspicion for infection is essential whenever there is clinical deterioration. Multi-drug resistant infections are frequently encountered with prolonged ICU stay, invasive lines, ventilation and renal replacement therapy. Since most of the infections in ALF are nosocomial, prevention of infections is crucial by infection control practices in the ICU. Although markers such as CRP, procalcitonin (for bacterial infections), 1,3-beta-D glucan, and galactomannan (fungal infections) aid in the diagnosis, the gold standard is blood culture. Therapy for respiratory infections must be based on BAL or mini-BAL culture. In this article, we discuss the common infections occurring in ALF, methods for early diagnosis and recommended prophylactic, pre-emptive as well as therapeutic options for treating infections in ALF.

Heterogenized dirhodium catalysts were prepared by anchoring the rhodium(II) trifluoroacetate dimer (Rh2(TFA)4) (TFA = trifluoroacetate) on the surface of the SBA-15 material bearing either amine or amine and carboxyl groups. After basic characterizations, the binding geometries of the catalysts were analyzed by 13C CP MAS and 15N CP MAS DNP NMR. 19F MAS NMR measurements were employed to quantify active catalyst sites in the heterogenized catalysts, which enables one to understand their catalytic performance in the cyclopropanation model between styrene and ethyl diazoacetate (EDA). The heterogeneous nature of the catalysts was confirmed by leaching and recyclability tests.

Background: As the size of the field effect transistors is reduced down to nanometers, the performance of the devices is affected by various short-channel effects. To overcome these effects, various novel devices are used. Tunnel Field Effect Transistors (TFET) are novel devices in which the drain current needs to be improved. Gate engineering and III-V compound materials are proposed to improve the ON current and reduce the leakage current along with its ambipolar behaviour.Methods: The proposed device structure is designed with a heterojunction hetero dielectric dual material gate Tunnel Field Effect Transistor incorporating various combinations of III-V compound materials such as AlGaAsSb/InGaAs, InGaAs/Ge, InGaAs/InP and SiGe/Si. As in III-V composite materials like AlGaAsSb/InGaAs, the narrower bandgap at the source channel interface helps to improve the electric field across the junction. At the same time, the wider bandgap at the channel drain junction leads to unidirectional current flow, resulting in ambipolar reduction. 2D TCAD simulation is used to obtain the electrical parameters for Hetero junction TFETs and the comparison analysis of different Hetero device structures.Results: The device's electrical parameters, such as energy band diagram, current density, electric field, drain current, gate capacitance and transconductance, have been simulated and analyzed. Besides, the dual material used in the gate, such as Metal1 (M1) and Metal2 (M2), along with HfO2/SiO2 stacked dielectric, helps improve the gate controllability over the channel and the leakage current reduction.Conclusion: An ION=10-1A/µm, IOFF = 10-12A/µm at drive voltage 0.5V is obtained for InGaAs/InP layer at the source channel hetero junction TFET, and ION=10-2A/µm, IOFF=10-14A/µm at drive voltage 0.5V is obtained for SiGe/Si layer at the source channel hetero junction TFET. Therefore, the InGaAs/InP and SiGe/Si layer TFET are more suitable for ultra-low power integrated circuits.

Arboviral transmission through transplanted organs is rare. We report a highly probable case of dengue viral transmission during live donor liver transplantation. Fever with severe thrombocytopenia was observed in the donor and recipient within 6 and 9 days after transplantation, respectively. Dengue diagnosis was confirmed by testing blood and explant tissue from the donor and recipient using dengue‐specific NAT(nucleic acid testing) and serology. Serology indicated the donor had secondary dengue infection that ran a mild course. However, the dengue illness in the recipient was severe and deteriorated rapidly, eventually proving fatal. The recipient's explant liver tissue tested negative for viral RNAindicative of a pretransplant naïve status. The prM–Envelope gene sequence analysis of the donor and recipient viral RNAidentified a similar serotype (DENV1) with almost 100% sequence identity in the envelope region. Molecular phylogenetic analysis of donor and recipient viral envelope sequences with regional and local dengue strains further confirmed their molecular similarity, suggesting a probable donor‐to‐recipient transmission via organ transplantation. Screening of living donors for dengue virus may be considered in endemic regions. The authors report a case of dengue viral transmission from donor to recipient in a live related liver transplant.

The predominant method to prepare polymer membranes is based on phase inversion. However, this method always leads to a dense skin with low porosity when normal polymers are used. Using the self-assembly of certain block copolymers, it is possible to prepare uniform pores with high porosity, but the prices of these polymers are too high to be afforded in practical applications. Here, we report a novel strategy to prepare highly porous and asymmetric polymer membranes using the widely used poly(vinylidene fluoride) (PVDF) as a prototype. The method combines spinodal decomposition with phase inversion utilizing mixed solvents that have the unique upper critical solution temperature phase behavior. The spinodal decomposition generates a thin surface layer containing a high density of relatively uniform pores in the mesoporous range, and the phase inversion generates a thick bulk layer composed of macrovoids; the two types of structures are interconnected, yielding a highly permeable, selective, and mechanically strong porous membrane. The membranes show an order of magnitude higher water permeance than commercial membranes and efficient molecular sieving of macromolecules. Notably, our strategy provides a general toolbox to prepare highly porous membranes from normal polymers. By blending PVDF with cellulose acetate (CA), a highly porous PVDF/CA membrane was prepared and showed similarly high separation performance, but the higher hydrophilicity of CA improved the membrane flux in the presence of proteins.

We demonstrated here a novel and facile synthesis of two-dimensional (2D) covalent organic thin film with pore size around 1.5 nm using a planar, amphiphilic and substituted heptacyclic truxene based triamine and a simple dialdehyde as building blocks by dynamic imine bond formation at the air/water interface using Langmuir–Blodgett (LB) method. Optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM), all unanimously showed the formation of large, molecularly thin and free-standing membrane that can be easily transferred on different substrate surfaces. The 2D membrane supported on a porous polysulfone showed a rejection rate of 64 and 71% for NaCl and MgSO4, respectively, and a clear molecular sieving at molecular size around 1.3 nm, which demonstrated a great potential in the application of pretreatment of seawater desalination and separation of organic molecules.

The investigation of V–Mo–W mixed oxide catalysts by 51V DNP MAS NMR is reported. It is shown that the 51V NMR signal from surface near vanadium nuclei was enhanced by a factor of ≈50 by direct polarization transfer from unpaired electrons to 51V nuclei. The dependency of the DNP enhancement of the samples on different polarizing mixtures is investigated and complemented by EPR studies. V–Mo–W mixed oxide catalysts with different stoichiometry (V2Mo8W0.5Oy,V2Mo8W1Oy, and V2Mo8W1.5Oy) are compared, and a suitable assignment of 51V signals to different phases that are present near to the catalysts surfaces is given. Finally, the applicability of DNP solid-state NMR for the characterization of V–Mo–W mixed oxide catalysts is discussed in terms of the synthesis conditions (i.e., pH-value).

Context:Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHRunderlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken.Objective:Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD,and TSHR) in CH cases with GIS.Patients, Design, and Setting:We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico.Results:Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG(12), TPO(four), DUOX2(two), and TSHR(one). Ten cases harbored triallelic (digenic) mutations: TGand TPO(one); SLC26A4and TPO(three), and DUOX2and TG(six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases.Conclusions:The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHRor known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TGor TPOmutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (∼41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated.

Background:Genetic susceptibility to insulin resistance is associated with lower adiposity in adults. Insulin resistance, and therefore adiposity, may alter sensitivity to GH. We aimed to determine the relationship between adiposity, genetic susceptibility to insulin resistance or insulin secretion, and response to GH treatment in short children born small for gestational age (SGA).Methods:In 89 short prepubertal SGA children (age, 6.2 ± 1.6 y; 55 boys) treated with GH for 1 year in a multicenter study, body fat percentage was estimated at baseline and 1 year using dual-energy x-ray absorptiometry. The main outcome measures were treatment-related changes in height, IGF-1 standard deviation score, insulin sensitivity, insulin secretion, and disposition index. Combined multiallele gene scores based on single nucleotide polymorphisms with known associations with lower insulin sensitivity (gene scores for insulin resistance [GS-InRes]) and insulin secretion (gene scores for insulin secretion [GS-InSec]) were analyzed for their relationships with adiposity.Results:Mean percentage body fat at baseline was low compared to normative data (P= .045) and decreased even further on GH treatment (baseline vs 1-year z-scores, −0.26 ± 1.2 vs −1.23 ± 1.54; P< .0001). Baseline percentage body fat was positively associated with IGF-1 responses (p-trends = .042), first-year height gains (B [95% confidence interval], 0.61 cm/y [0.28,0.95]; P< .0001), insulin secretion at baseline (p-trends = .020) and 1 year (p-trends = .004), and disposition index at 1 year (p-trends = .024). GS-InRes was inversely associated with body mass index (−0.13 SD score per allele [−0.26, −0.01]; P= .040), body fat (−0.49% per allele [−0.97, −0.007]; P= .047), and limb fat (−0.81% per allele [−1.62, 0.00]; P= .049) at baseline. During GH treatment, GS-InRes was related to a lesser decline in trunk fat (0.38% per allele [0.16, 0.59]; P= .001) and a higher trunk-limb fat ratio at 1 year (0.04 per allele [0.01, 0.08]; P= .008). GS-InSec was positively associated with truncal fat (0.36% per allele [0.09, 0.63]; P= .009).Conclusions:Adiposity in SGA children has favorable effects on GH sensitivity and glucose metabolism. The associations with multiallele scores support a causal role of insulin resistance in linking lesser body fat to reduced sensitivity to exogenous GH.

Congenital anomalies may be associated with Wilms tumor either as isolated anomalies or as part of a congenital malformation syndrome. Nephroblastoma occurring in association with polycystic kidneys is very rare. The optimal surgical management of nephroblastoma in the setting of polycystic kidneys is not defined because of the rarity of this presentation. PHACE syndrome includes posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of aorta, and eye abnormalities. We report a 17-month-old baby with bilateral polycystic kidneys and PHACE syndrome who developed nephroblastoma in the right polycystic kidney which was treated successfully with nephron-sparing partial nephrectomy and chemotherapy.

Catalytically active dirhodium sheet-like coordination polymers are synthesized from their precursors vialigand exchange. The individual lamellae of the dirhodium-bdc frameworks are stacked as parallel sheets, which are randomly oriented or slightly ordered. As inorganic building blocks Rh2(TFA)4and Rh2(OAc)4, and as organic linker benzene 1,4-dicarboxylate (bdc) are employed. The successful synthesis of the Rh2-bdc(Tf) and Rh2-bdc(Ac) catalysts is proven by ATR-IR, XPS and 13C CP MAS NMR. Residual trifluoroacetate species are investigated by quantitative 19F MAS NMR which further reflects the configuration of trifluoroacetate in the obtained Rh2-bdc(Tf), and defects in the structure. DR-UV-vis and XPS demonstrate that the oxidation state and the Rh–Rh single bond in the dirhodium node are maintained during the ligand substitution process. The stability and reusability of the catalysts are verified by TG-DTA measurements and leaching tests. The catalysts show similar catalytic efficiency as the homogeneous catalyst in the model cyclopropanation between ethyl diazoacetate (EDA) and styrene.

We investigated the potential of solid-state NMR using magic angle spinning (MAS) with and without dynamic nuclear polarization (DNP) and electron paramagnetic resonance (EPR) for the characterization of functionalized nanodiamonds (NDs). We showed that conventional 1H, 31P, and 13C solid-state NMR spectra allow differentiating in a straightforward way NDs from commercial sources and custom-made NDs bearing aromatic or aliphatic phosphonate moieties at their surface. Besides, the short nuclear relaxation times prove the close proximity between the endogenous paramagnetic centers of NDs and the grafted organic moieties. EPR spectra confirmed the presence of these paramagnetic centers in functionalized NDs, which are centered on dangling bonds as well as a few N0defects, corresponding to the substitution of carbon atoms by nitrogen ones. Hyperfine sublevel correlation spectroscopy indicates that the N0paramagnetic centers are mostly located in the disordered shell of NDs. Preliminary DNP-enhanced NMR experiments at 9.4 T and 100 K under MAS have shown a lack of significant DNP enhancement, which can be attributed to the short relaxation times of the unpaired electrons and the nuclei in NDs. When using exogenous polarizing agents, the endogenous unpaired electrons contribute to a leakage of polarization. Furthermore, low temperatures lead to a broadening of NMR signals. It therefore appears that conventional direct excitation remains the NMR method of choice for the characterization of functionalized NDs.

Lithium–sulfur batteries suffer from severe self-discharge due to polysulfide dissolution into electrolytes. In this work, a chemically anchored polymer-coated (CAPC) sulfur electrode was prepared, through chemical bonding by coordinated Cu ions and cross-linking, to improve cyclability for Li/S batteries. This electrode retained specific capacities greater than 665 mAh g–1at high current density of 3.35 A g–1(2Crate) after 100 cycles with an excellent Coulombic efficiency of 100%.

We show that dynamic nuclear polarization (DNP) can be used to enhance NMR signals of 13C and 29Si nuclei located in mesoporous organic/inorganic hybrid materials, at several hundreds of nanometers from stable radicals (TOTAPOL) trapped in the surrounding frozen disordered water. The approach is demonstrated using mesoporous silica nanoparticles (MSN), functionalized with 3-(N-phenylureido)propyl (PUP) groups, filled with the surfactant cetyltrimethylammonium bromide (CTAB). The DNP-enhanced proton magnetization is transported into the mesopores via 1H–1H spin diffusion and transferred to rare spins by cross-polarization, yielding signal enhancements εon/offof around 8. When the CTAB molecules are extracted, so that the radicals can enter the mesopores, the enhancements increase to εon/off≈ 30 for both nuclei. A quantitative analysis of the signal enhancements in MSN with and without surfactant is based on a one-dimensional proton spin diffusion model. The effect of solvent deuteration is also investigated.

To undertake a multidisciplinary characterisation of the phenotype associated with SOX11variants.

Background: Pegvisomant is a genetically engineered molecule, which exhibits specific growth hormone (GH) antagonism by directly interacting with the GH receptor. It is currently licensed for the treatment of acromegaly where surgery and medical therapy with somatostatin analogues have failed. Objective: To delineate the role of pegvisomant in the treatment of acromegaly and its novel application in other areas of clinical medicine where suppression of GH action may be of therapeutic benefit. Methods: A literature review from PubMed- and EMBASE-listed publications and the web-sites of licensing organisations for medicinal products. Conclusion: Pegvisomant is currently used as a second line therapy in the management of acromegaly. It is highly effective in suppressing the metabolic effects of elevated GH levels when used alone or in combination with somatostatin analogues. However, its long term efficacy and safety for this indication has yet to be established. Preliminary data indicate that pegvisomant may have a role in management of type 1 diabetes with beneficial effects on insulin sensitivity and in preventing the progression of microvascular complications. Additional roles as an adjunct to cancer chemotherapy regimens and for the diagnosis of GH deficiency have been proposed, but have yet to be confirmed.