Cadaveric small bowel and small bowel-liver transplantation in humans

Five patients had complete cadaveric small bowel transplants under FK506 immunosuppression, one as an isolated graft and the other 4 in continuity with a liver. Three were children and two were adults. The five patients are living 2-13 months posttransplantation with complete alimentation by the intestine. The typical postoperative course was stormy, with sluggish resumption of gastrointestinal function. The patient with small intestinal transplantation alone had the most difficult course of the five, including two severe rejections, bacterial and fungal translocation with bacteremia, renal failure with the rejections, and permanent consignment to renal dialysis. The first four patients (studies on the fifth were incomplete) had replacement of the lymphor-eticular cells in the graft lamina propria by their own lymphoreticular cells. Although the surgical and aftercare of these patients was difficult, the eventual uniform success suggests that intestinal transplantation has moved toward becoming a practical clinical service. © 1992 by Williams and Wilkins

Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner

The blood vessels of cancerous tumours are leaky and poorly organized. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less leaky—have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights, but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here, we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12 nm) while hindering the delivery of larger nanoparticles (diameter, 125 nm). Using a mathematical model, we show that reducing the sizes of pores in the walls of vessels through normalization decreases the interstitial fluid pressure in tumours, thus allowing small nanoparticles to enter them more rapidly. However, increased steric and hydrodynamic hindrances, also associated with smaller pores, make it more difficult for large nanoparticles to enter tumours. Our results further suggest that smaller (~12 nm) nanomedicines are ideal for cancer therapy due to their superior tumour penetration.ImClone Systems IncorporatedNational Institutes of Health (U.S.) (P01-CA080124)National Institutes of Health (U.S.) (R01-CA126642)National Institutes of Health (U.S.) (R01-CA115767)National Institutes of Health (U.S.) (R01-CA096915)National Institutes of Health (U.S.) (R01-CA085140)National Institutes of Health (U.S.) (R01-CA098706)National Institutes of Health (U.S.) (T32-CA073479)United States. Dept. of Defense (Breast Cancer Research Innovator Award W81XWH-10-1-0016

Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films

Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B$^+$) and phosphorous (P$^+$) ions. Different samples, prepared by varying the ion dose in the range $10^{14}$ to 5 x $10^{15}$ and ion energy in the range 150-350 keV, were investigated by the Raman spectroscopy, photoluminescence (PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman results from dose dependent B$^+$ implanted samples show red-shifted and asymmetrically broadened Raman line-shape for B$^+$ dose greater than $10^{14}$ ions cm$^{-2}$. The asymmetry and red shift in the Raman line-shape is explained in terms of quantum confinement of phonons in silicon nanostructures formed as a result of ion implantation. PL spectra shows size dependent visible luminescence at $\sim$ 1.9 eV at room temperature, which confirms the presence of silicon nanostructures. Raman studies on P$^+$ implanted samples were also done as a function of ion energy. The Raman results show an amorphous top SOS surface for sample implanted with 150 keV P$^+$ ions of dose 5 x $10^{15}$ ions cm$^{-2}$. The nanostructures are formed when the P$^+$ energy is increased to 350 keV by keeping the ion dose fixed. The GAXRD results show consistency with the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in SILICON(SPRINGER

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic response

Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic respons

MIA-Prognosis: A Deep Learning Framework to Predict Therapy Response

Predicting clinical outcome is remarkably important but challenging. Research efforts have been paid on seeking significant biomarkers associated with the therapy response or/and patient survival. However, these biomarkers are generally costly and invasive, and possibly dissatifactory for novel therapy. On the other hand, multi-modal, heterogeneous, unaligned temporal data is continuously generated in clinical practice. This paper aims at a unified deep learning approach to predict patient prognosis and therapy response, with easily accessible data, e.g., radiographics, laboratory and clinical information. Prior arts focus on modeling single data modality, or ignore the temporal changes. Importantly, the clinical time series is asynchronous in practice, i.e., recorded with irregular intervals. In this study, we formalize the prognosis modeling as a multi-modal asynchronous time series classification task, and propose a MIA-Prognosis framework with Measurement, Intervention and Assessment (MIA) information to predict therapy response, where a Simple Temporal Attention (SimTA) module is developed to process the asynchronous time series. Experiments on synthetic dataset validate the superiory of SimTA over standard RNN-based approaches. Furthermore, we experiment the proposed method on an in-house, retrospective dataset of real-world non-small cell lung cancer patients under anti-PD-1 immunotherapy. The proposed method achieves promising performance on predicting the immunotherapy response. Notably, our predictive model could further stratify low-risk and high-risk patients in terms of long-term survival.Comment: MICCAI 2020 (Early Accepted; Student Travel Award

Isolated Splenic Metastasis from Rectal Carcinoma: A Rare Occurrence

The presence of isolated splenic metastasis in rectal carcinoma is uncommon and usually presents as an asymptomatic mass, noted incidentally on imaging. Splenectomy is usually performed with the goal of curing metastatic disease. It is unclear if adjuvant chemotherapy affords any benefit, and the prognosis is unknown. The case of a young woman is reported, in whom an isolated metastatic lesion in the spleen was discovered 9 months after adjuvant chemotherapy for stage III rectal adenocarcinoma. The patient has remained disease-free for nearly 5 years following splenectomy and chemotherapy. To our knowledge, this is the fourth reported case in the English literature of an isolated splenic metastatic lesion from rectal cancer. We discuss the unique presentation, the importance of post-treatment surveillance, and the implementation of multi-modality treatment strategies in this young patient