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Silicon-photonics based high volume manufacturable lasers are playing an increasingly important role in optical communication and sensing due to their low-cost, high performance, and seamless integration with other silicon photonics components. Here we demonstrate a silicon-photonics based widely tunable laser with integrated semiconductor optical amplifier (SOA) and wavelength reference on a high-volume, 300-mm III-V/Si integration platform. The laser shows a tuning range >50 nm with side-mode suppression ratio >55 dB, Lorentzian linewidth <30 kHz, and relative intensity noise (RIN) <−150 dB/Hz across the entire tuning range. We also demonstrate an active control of the laser. When locked to an external wavelength reference, the laser shows a frequency error <1 GHz against changes to the chip temperature. Amplified by an SOA, the on-chip optical power exceeds 17 dBm. Such tunable lasers can be integrated with other silicon-based photonic components including high-speed modulators and detectors for a variety of applications, ranging from optical communication to sensing.

End-stage renal disease (ESRD) is a significant health care burden. Although kidney transplantation is the optimal treatment modality, less than 25% of waiting list patients are transplanted because of organ shortage. Living kidney donation can lead to better recipient and graft survival and increase the number of donors. Not all ESRD patients have potential living donors, and not all living donors are a compatible match to recipients. Kidney paired exchanges allow incompatible pairs to identify compatible living donors for living donor kidney transplants for multiple recipients. Innovative modifications of kidney paired donation can increase the number of kidney transplants, with excellent outcomes.

Since the implementation of the Model of End-stage Liver Disease score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of postliver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post-LT AKI which then predisposes to posttransplant chronic kidney disease. Prevention of posttransplant AKI is essential in the improvement of long-term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate. New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post-LT in patients with early posttransplant AKI may improve glomerular filtration rate in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late chronic kidney disease.The authors provide a comprehensive review of the current understanding of acute kidney injury in liver transplant patients. Guidelines for prevention and treatment of acute kidney injury are provided based on a systematic literature review and expert opinion.

The authors investigate the cellular and humoral immune responses in an allogeneic hepatocytes transplantation model, suggesting that more effective immunotherapeutic strategies are necessary to target both unique CD8-mediated immune responses primed in the liver and conventional alloimmune rejection pathways.

The authors demonstrate that mTOR inhibitor, not calcineurin inhibitor, directly suppresses alloantibody production by alloprimed IgG1+ B cells and delays graft rejection in a mice model with hepatocytes transplantation. Supplemental digital content is available in the text.

INTRODUCTION: Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed. OBJECTIVE: To determine the efficacy of liver transplant in children with HBL or HCC. DESIGN, PARTICIPANTS, AND SETTING: This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria. MAIN OUTCOMES AND MEASURES: Disease-free and overall patient survival and graft survival. RESULTS: Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence. CONCLUSIONS AND RELEVANCE: Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8T cell–mediated acute rejection pathways. The magnitude of allospecific CD8T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4T cells. The current studies were conducted to determine if and how CD4T cells might influence cytotoxic effector mechanisms.

Abstract: Background: EsophyX is an endolumenal approach to the treatment of gastroesophageal reflux disease (GERD). This report describes one of the earliest and largest North American experiences with this device. Methods: Prospective data were gathered on consecutive patients undergoing EsophyX fundoplication for a 1-year period between September 2007 and March 2009. During this time, the procedure evolved to the current technique. A P value less than 0.05 was considered significant. Results: The study enrolled 26 patients with a mean age of 45 years. The patients included 16 women (62%) with a mean body mass index (BMI) of 28 and an American Society Anesthesiology (ASA) classification of 2. These patients included 11 with associated small hiatal hernias, 3 with Barrett’s esophagus, and 5 with esophageal dysmotility. The procedure time was 65 min (range, 29–137 min), and the length of hospital stay was 1 day (range, 0–6 days). The postoperative valve circumference was 217º, and the valve length was 2.7 cm. Two complications of postoperative bleed occurred, requiring transfusion. The mean follow-up period was 10 months. Comparison of pre- and postoperative Anvari scores (34–17; P = 0.002) and Velanovich scores (22–10; P = 0.0007) showed significant decreases. Although 68% of the patients were still taking antireflux medications, 21% had reduced their dose by half. Three patients had persistent symptoms requiring Nissen fundoplication, and there was one late death unrelated to the procedure. Conclusion: This study represents an initial single-institution experience with EsophyX. According to the findings, 53% of the patients had either discontinued their antireflux medication (32%) or had decreased their dose by half (21%). Both symptoms and health-related quality-of-life (HRQL) scores significantly improved after treatment. Further follow-up evaluation and objective testing are required.

Galanin affects gastrointestinal functions by activating different G protein–coupled receptors. Here, we identified the sites of expression of the galanin receptor 1 (GAL‐R1) subtype in the rat stomach and small intestine by using immunohistochemistry with an antibody raised to the third intracellular loop of rat GAL‐R1 (GAL‐R1Y225‐238) and confocal microscopy. Antibody specificity was confirmed by (1) the detection of a band at approximately 70 kDa in Western blot of membranes from GAL‐R1 transfected cells, (2) the cell surface staining of GAL‐R1 transfected cells, which was not detected in control cells, and (3) the abolition of Western signal and tissue immunostaining by preadsorbing the antibody with the peptide used for immunization. GAL‐R1 immunoreactivity was localized to the cell surface of enterochromaffin‐like cells, and of myenteric and submucous neurons, and to fibers distributed to the plexuses, interconnecting strands, muscle layers, vasculature, and mucosa. A dense network of GAL‐R1 immunoreactivity was observed in the deep muscular plexus in very close association with interstitial cells of Cajal visualized by c‐kit immunostaining. In the ileum, 81.6% of GAL‐R1 myenteric neurons and 70.7% of GAL‐R1 submucosal neurons were substance P immunoreactive. Vasoactive intestinal polypeptide immunoreactivity was found in 48.3% of GAL‐R1 submucosal neurons, but not in GAL‐R1 myenteric neurons. These findings support the hypothesis that GAL‐R1 mediates galanin actions on gastrointestinal motility and secretion by modulating the release of other neurotransmitters and contributes to galanin‐induced inhibition of gastric acid secretion by means of the suppression of endogenous histamine release. J. Comp. Neurol. 450:292–302, 2002. © 2002 Wiley‐Liss, Inc.

The goal of this study was to engineer gastrin-producing G cells of the gastric antrum to produce insulin. A pGas-Ins chimeric gene in which the gastrin promoter drives expression of the human insulin gene was constructed and was validated by transient transfection of GH4 and AGS cells. RT-PCR analysis and sequencing revealed three forms of differentially spliced insulin mRNA in GH4 cells transiently transfected by pGas-Ins. Gas-Ins transgenic mice were generated utilizing this chimeric gene. Northern blot analysis, in situhybridization, and immunohistochemistry demonstrated expression of the human insulin gene specifically in antral G cells. Northern blot analysis demonstrated that the shortest of the insulin mRNA three forms is predominantly expressed in stomach tissue. RT-PCR analysis also showed expression of the transgene in colon, pancreas, and brain tissues that was undetectable by northern analysis. We conclude that gastrin promoter can be used for targeting expression of human insulin to antral G cells and that antral G cells can express human insulin. Further refining of the chimeric gene design is required to enhance expression.

Persistent mixed chimerism protects against rejection of HLA-matched and mismatched kidney transplants without graft-versus-host disease.