Cystic fibrosis associated liver disease in children

Cystic fibrosis(CF)is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator gene.CF liver disease develops in 5%-10%of patients with CF and is the third leading cause of death among patients with CF after pulmonary disease or lung transplant complications.We review the pathogenesis,clinical presentations,complications,diagnostic evaluation,effect of medical therapies especially CF transmembrane conductance regulator modulators and liver transplantation in CF associated liver disease.

Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in cystic fibrosis patients

BACKGROUND Hepatic steatosis is a common form of cystic fibrosis associated liver disease(CFLD)seen in an estimated 15%-60%of patients with cystic fibrosis(CF).The pathophysiology and health implications of hepatic steatosis in cystic fibrosis remain largely unknown.In the general population,hepatic steatosis is strongly associated with insulin resistance and type 2 diabetes.Cystic fibrosis related diabetes(CFRD)impacts 40%-50%of CF adults and is characterized by both insulin insufficiency and insulin resistance.We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than cystic fibrosis patients without diabetes.AIM To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF.METHODS Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study.Only pancreatic insufficient patients with CFRD or normal glucose tolerance(NGT)were included.Patients with established CFLD,end stage lung disease,or persistently elevated liver enzymes were excluded.Mean magnetic resonance imaging(MRI)proton density fat fraction(PDFF)was obtained for all participants.Clinical characteristics[age,sex,body mass index,percent predicted forced expiratory volume at 1 s(FEV1),lumacaftor/ivacaftor use]and blood chemistries were assessed for possible association with hepatic steatosis.Hepatic steatosis was defined as a mean MRI PDFF>5%.Patients were grouped by diabetes status(CFRD,NGT)and cystic fibrosis transmembrane conductance regulator(CFTR)modulator use(lumacaftor/ivacaftor,no lumacaftor/ivacaftor)to determine between group differences.Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher’s exact test.RESULTS Twenty subjects were included in the final analysis.The median age was 22.3 years(11.3-39.0)and median FEV1 was 77%(33%-105%).Twelve subjects had CFRD and 8 had NGT.Nine subjects were receiving lumacaftor/ivacaftor.The median PDFF was 3.0%(0.0%-21.0%).Six subjects(30%)had hepatic steatosis defined as PDFF>5%.Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor(median,range)(2.0%,0.0%-6.4%)than in patients not receiving lumacaftor/ivacaftor(4.1%,2.7-21.0%),P=0.002.Though patients with CFRD had lower PDFF(2.2%,0.0%-14.5%)than patients with NGT(4.9%,2.4-21.0%)this did not reach statistical significance,P=0.06.No other clinical characteristic was strongly associated with hepatic steatosis.CONCLUSION Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis.No association between CFRD and hepatic steatosis was found in this cohort.

A high voltage silicon-on-insulator lateral insulated gate bipolar transistor with a reduced cell-pitch

A high voltage（〉 600 V） integrable silicon-on-insulator（SOI） trench-type lateral insulated gate bipolar transistor（LIGBT） with a reduced cell-pitch is proposed.The LIGBT features multiple trenches（MTs）：two oxide trenches in the drift region and a trench gate extended to the buried oxide（BOX）.Firstly,the oxide trenches enhance electric field strength because of the lower permittivity of oxide than that of Si.Secondly,oxide trenches bring in multi-directional depletion,leading to a reshaped electric field distribution and an enhanced reduced-surface electric-field（RESURF） effect.Both increase the breakdown voltage（BV）.Thirdly,oxide trenches fold the drift region around the oxide trenches,leading to a reduced cell-pitch.Finally,the oxide trenches enhance the conductivity modulation,resulting in a high electron/hole concentration in the drift region as well as a low forward voltage drop（Von）.The oxide trenches cause a low anode-cathode capacitance,which increases the switching speed and reduces the turn-off energy loss（Eoff）.The MT SOI LIGBT exhibits a BV of 603 V at a small cell-pitch of 24 μm,a Von of 1.03 V at 100 A/cm-2,a turn-off time of 250 ns and Eoff of 4.1×10？3 mJ.The trench gate extended to BOX synchronously acts as dielectric isolation between high voltage LIGBT and low voltage circuits,simplifying the fabrication processes.

Conductivity modulation enhanced lateral IGBT with SiO_2 shielded layer anode by SIMOX technology on SOI substrate

A new lateral insulated-gate bipolar transistor（LIGBT） with a SiO_2 shielded layer anode on SOI substrate is proposed and discussed.Compared to the conventional LIGBT,the proposed device offers an enhanced conductivity modulation effect due to the SiO_2 shielded layer anode structure which can be formed by SIMOX technology.Simulation results show that,for the proposed LIGBT,during the conducting state,the electron-hole plasma concentrations in the n-drift region are several times larger than those of the conventional LIGBT;the conducting current is up to 37% larger than that of the conventional one.The enhanced conductivity modulation effect by SiO_2 shielded layer anode does not sacrifice other characteristics of the device,such as breakdown and switching,but is compatible with other optimized technologies.

First demonstration of a self-aligned p-channel GaN back gate injection transistor

In this study,we present the development of self-aligned p-channel Ga N back gate injection transistors(SA-BGITs)that exhibit a high ON-state current.This achievement is primarily attributed to the conductivity modulation effect of the 2-D electron gas(2DEG,the back gate)beneath the 2-D hole gas(2DHG)channel.SA-BGITs with a gate length of 1μm have achieved an impressive peak drain current(I_(D,MAX))of 9.9 m A/mm.The fabricated SA-BGITs also possess a threshold voltage of 0.15 V,an exceptionally minimal threshold hysteresis of 0.2 V,a high switching ratio of 10~7,and a reduced ON-resistance(RON)of 548Ω·mm.Additionally,the SA-BGITs exhibit a steep sub-threshold swing(SS)of 173 mV/dec,further highlighting their suitability for integration into Ga N logic circuits.

A high-conductivity insulated gate bipolar transistor with Schottky hole barrier contact

This letter proposes a high-conductivity insulated gate bipolar transistor （HC-IGBT） with Schottky con- tact formed on the p-base, which forms a hole barrier at the p-base side to enhance the conductivity modulation effect. TCAD simulation shows that the HC-IGBT provides a current density increase by 53% and turn-off losses decrease by 27% when compared to a conventional field-stop IGBT （FS-IGBT）. Hence, the proposed IGBT exhibits superior electrical performance for high-efficiency power electronic systems.

An insulated gate bipolar transistor with surface n-type barrier

This letter proposes a novel IGBT structure with an n-type barrier （NB-IGBT） formed on the silicon surface to enhance the conductivity modulation effect with a relatively simple fabrication process. TCAD simulation indicates that the NB-IGBT offers a current density 49% higher and turn-off losses 25% lower than a conventional field-stop IGBT （FS-IGBT） with a similar breakdown voltage, turn-off time and avalanche energy. Furthermore, the NB-IGBT exhibits extremely large transconductance, which is favorable to turn-on and turn-off. Therefore, the proposed IGBT offers an attractive option for high-voltage and large-power electronics applications.

Physical effect on transition from blocking to conducting state of barrier-type thyristor

The transition of the barrier-type thyristor （BTH） from blocking to conducting-state occurs between two entirely contrary physical states with great disparity in nature. The physical effects and mechanisms of the transition are studied in depth. The features of the transition snapback point are analyzed in detail. The transition snapback point has duality and is just the position where the barrier is flattened. It has a significant influence on the capture crosssection of the hole and high-level hole lifetime, resulting in the device entering into deep base conductance modulation. The physical nature of the negative differential resistance segment I-V characteristics is studied. It is testified by using experimental data that the deep conductance modulation is the basic feature and the linchpin of the transition process. The conditions and physical mechanisms of conductance modulation are investigated. The related physical subjects, including the flattening of the channel barrier, the buildup of the double injection, the formation of the plasma, the realization of the high-level injection, the elimination of the gate junction depletion region, the deep conductance modulation, and the increase in the hole＇s lifetime are all discussed in this paper.