Quantum circuits with many photons on a programmable nanophotonic chip.

Growing interest in quantum computing for practical applications has led to a surge in the availability of programmable machines for executing quantum algorithms1,2. Present-day photonic quantum computers3-7 have been limited either to non-deterministic operation, low photon numbers and rates, or fixed random gate sequences. Here we introduce a full-stack hardware-software system for executing many-photon quantum circuit operations using integrated nanophotonics: a programmable chip, operating at room temperature and interfaced with a fully automated control system. The system enables remote users to execute quantum algorithms that require up to eight modes of strongly squeezed vacuum initialized as two-mode squeezed states in single temporal modes, a fully general and programmable four-mode interferometer, and photon number-resolving readout on all outputs. Detection of multi-photon events with photon numbers and rates exceeding any previous programmable quantum optical demonstration is made possible by strong squeezing and high sampling rates. We verify the non-classicality of the device output, and use the platform to carry out proof-of-principle demonstrations of three quantum algorithms: Gaussian boson sampling, molecular vibronic spectra and graph similarity8. These demonstrations validate the platform as a launchpad for scaling photonic technologies for quantum information processing.

Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group.

BACKGROUND: The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells and are under clinical trial development. However, the optimisation and standardisation of neoantigen identification, as well as its delivery as immunotherapy are needed to increase tumour-specific T-cell responses and, thus, the clinical efficacy of current cancer immunotherapies. METHODS: In this recommendation article, launched by the European Society for Medical Oncology (ESMO), we outline and discuss the available framework for neoantigen prediction and present a systematic review of the current scientific evidence. RESULTS: A number of computational pipelines for neoantigen prediction are available. Most of them provide peptide major histocompatibility complex (MHC) binding affinity predictions, but more recent approaches incorporate additional features like variant allele fraction, gene expression, and clonality of mutations. Neoantigens can be predicted in all cancer types with high and low tumour mutation burden, in part by exploiting tumour-specific aberrations derived from mutational frameshifts, splice variants, gene fusions, endogenous retroelements and other tumour-specific processes that could yield more potently immunogenic tumour neoantigens. Ongoing clinical trials will highlight those cancer types and combinations of immune therapies that would derive the most benefit from neoantigen-based immunotherapies. CONCLUSIONS: Improved identification, selection and prioritisation of tumour-specific neoantigens are needed to increase the scope of benefit from cancer vaccines and adoptive T-cell therapies. Novel pipelines are being developed to resolve the challenges posed by high-throughput sequencing and to predict immunogenic neoantigens.

Herbal feed additives containing essential oil: 1. Impact on the nutritional worth of complete feed in vitro.

This study was taken up to assess the impact of supplementing herbal feed additives [HFAs; fruit of Myristica fragrans (Jayphall), seeds of Anethum sowa (Suva), fruit of Apium graveolens (Ajmo), fruit of Cuminum cyminum (Jeera), bark of Cinnamonum zeylanicum (Dalchini), or whole plant of Eclipta alba (Bhangro)] containing essential oils as active component on the nutrient utilization and methane production using wheat straw-based total mixed ration (TMR) as a substrate by in vitro gas production technique. The essential oil content was the highest (P < 0.01) in M. fragrans followed by E. alba and A. sowa. In addition to essential oils, these HFAs also contained saponins, tannins, and antioxidants. The HFAs were supplemented at 1-3% of substrate dry matter (DM). The data were analyzed by 6 × 4 factorial design. Irrespective of level of HFA, the net gas production (NGP) and metabolizable energy (ME) availability was the highest (P < 0.01) in TMR supplemented with C. zeylanicum comparable with E. alba, but higher than TMR supplemented with other HFAs. Supplementation of TMR with different HFAs did not affect the digestibility of neutral detergent fiber (NDF) and true organic matter (TOM) and partitioning factor (PF). The total volatile fatty acids (VFAs), acetate, propionate (P < 0.01), and butyrate (P < 0.05) production was the highest in TMR supplemented with A. sowa, and the lowest was observed in TMR supplemented with C. cyminum. The isobutyrate and valerate production was also the highest (P < 0.01) in diet supplemented with A. sowa, but isovalerate production was the highest (P < 0.01) in diet supplemented with C. zeylanicum. The A:P ratio was the best in TMR supplemented with A. sowa. The efficiency of rumen fermentation was the highest, and efficiency of conversion of hexose to methane was the lowest in diet supplemented with A. sowa as compared to all other supplements. The in vitro methane production expressed as either percent of NGP, ml/100 mg DM of substrate/24 h, or as ml/100 mg of digestible OM/24 h was the lowest in TMR supplemented with A. sowa. The ammonia nitrogen production from TMR supplemented with M. fragrans and A. sowa was comparable, but significantly (P < 0.01) lower than TMR supplemented with other HFAs. Irrespective of the nature of HFA, the NGP and ME availability were significantly (P < 0.01) higher in TMR supplemented with HFAs at all levels as compared to un-supplemented TMR. As compared to control, the digestibility of NDF and that of TOM was depressed slightly in all the HFA-supplemented TMRs. The supplementation of HFAs at 2% of substrate DM improved (P < 0.01) the production of total VFAs, acetate, and propionate, and that of isovalerate in comparison to the un-supplemented TMR. The acetate to propionate ratio increased (P < 0.01) with the increase in the level of supplementation of HFAs containing essential oils. The methane and ammonia productions were depressed significantly when TMR was supplemented at 2% level of HFAs as compared to control TMR. It was concluded that supplementation of TMR with A. sowa at 2% of substrate was fermented better as indicated by the production of total and individual VFA, methane, and ammonia as compared to TMR supplemented with other HFA or un-supplemented TMR.

Genomic characterization of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy-results from the ACOSOG Z1041 (Alliance) trial.

Background: HER2 (ERBB2) gene amplification and its corresponding overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents are effective treatments, resistance remains a major cause of death. The American College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to compare the pathologic complete response (pCR) rate of distinct regimens of neoadjuvant chemotherapy and trastuzumab, but ultimately identified no difference. Patients and methods: In supplement to tissues from 37 Z1041 cases, 11 similarly treated cases were obtained from a single institution study (NCT00353483). We have extracted genomic DNA from both pre-treatment tumor biopsies and blood of these 48 cases, and performed whole genome (WGS) and exome sequencing. Coincident with these efforts, we have generated RNA-seq profiles from 42 of the tumor biopsies. Among patients in this cohort, 24 (50%) achieved a pCR. Results: We have characterized the genomic landscape of HER2-positive breast cancer and investigated associations between genomic features and pCR. Cases assigned to the HER2-enriched subtype by RNA-seq analysis were more likely to achieve a pCR compared to the luminal, basal-like, or normal-like subtypes (19/27 versus 3/15; P = 0.0032). Mutational events led to the generation of putatively active neoantigens, but were overall not associated with pCR. ERBB2 and GRB7 were the genes most commonly observed in fusion events, and genomic copy number analysis of the ERBB2 locus indicated that cases with either no observable or low-level ERBB2 amplification were less likely to achieve a pCR (7/8 versus 17/40; P = 0.048). Moreover, among cases that achieved a pCR, tumors consistently expressed immune signatures that may contribute to therapeutic response. Conclusion: The identification of these features suggests that it may be possible to predict, at the time of diagnosis, those HER2-positive breast cancer patients who will not respond to treatment with chemotherapy and trastuzumab. ClinicalTrials.gov identifiers: NCT00513292, NCT00353483.

Amyloid Deposition of the Bilateral Ureters in a Patient With Chronic Systemic AL Amyloidosis.

Amyloid of the ureter is a rare disease with less than 25 cases reported in the literature. Despite being rare, it remains an important entity as it is typically confused with a primary neoplastic process of the urinary system. We report a case of a 68-year-old male with a history of cutaneous amyloid with late presentation of bilateral ureteral involvement.

Integrative rehabilitation of residents chronic post-stroke in skilled nursing facilities: the design and evaluation of the BrightArm Duo.

PURPOSE: To describe the novel BrightArm Duo bimanual upper extremity (UE) rehabilitation system; to determine its technology acceptance and clinical benefit for older hemiplegic participants. METHODS: The system table tilted to adjust arm gravity loading. Participants wore arm supports that sensed grasp strength and wrist position on the table. Wrist weights further increased shoulder exertion. Games were designed to improve UE strength, motor function, cognition and emotive state and adapted automatically to each participant. The system underwent feasibility trials spanning 8 weeks in two skilled nursing facilities (SNFs). Participants were evaluated pre-therapy and post-therapy using standardized clinical measures. Computerized measures of supported arm reach, table tilt and number of arm repetitions were stored on a remote server. OUTCOMES: Seven participants had significant improvements in their active range of shoulder movement, supported arm reach, shoulder strength, grasp strength and their ability to focus. The group demonstrated higher arm function measured with FMA (p = 0.01) and CAHAI (p = 0.05), and had an improvement in depression (Becks Depression Inventory, II). BrightArm Duo technology was well accepted by participants with a rating of 4.4 out of 5 points. CONCLUSIONS: Given these findings, it will be beneficial to evaluate the BrightArm Duo application in SNF maintenance programs. Implications for Rehabilitation Integrative rehabilitation that addresses both physical and cognitive domains is promising for post-stroke maintenance in skilled nursing facilities. Simultaneous bilateral arm exercise may improve arm function in older hemiplegic patients several years after stroke. Virtual reality games that adapt to the patient can increase attention and working memory while decreasing depression in elderly.

U2AF1 mutations alter sequence specificity of pre-mRNA binding and splicing.

We previously identified missense mutations in the U2AF1 splicing factor affecting codons S34 (S34F and S34Y) or Q157 (Q157R and Q157P) in 11% of the patients with de novo myelodysplastic syndrome (MDS). Although the role of U2AF1 as an accessory factor in the U2 snRNP is well established, it is not yet clear how these mutations affect splicing or contribute to MDS pathophysiology. We analyzed splice junctions in RNA-seq data generated from transfected CD34+ hematopoietic cells and found significant differences in the abundance of known and novel junctions in samples expressing mutant U2AF1 (S34F). For selected transcripts, splicing alterations detected by RNA-seq were confirmed by analysis of primary de novo MDS patient samples. These effects were not due to impaired U2AF1 (S34F) localization as it co-localized normally with U2AF2 within nuclear speckles. We further found evidence in the RNA-seq data for decreased affinity of U2AF1 (S34F) for uridine (relative to cytidine) at the e-3 position immediately upstream of the splice acceptor site and corroborated this finding using affinity-binding assays. These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis.

S M R of inferior turbinate in chronic hypertrophic rhinitis.

A study was undertaken to evaluate the role of unilatcral/bilateral submucous resection of the inferior turbinates in fifty cases of chronic hypertrophic rhinitis. Patients associated with deflected nasal septum or sinus infectious were excluded from the study. Decongesiton of turbinates was done to exclude the cases with predominantly mucosal hypertrophy. Gertner (1984) plate method was used to asses the nasal patency preoperatively and then post-operatively at 1, 3 and 6 months follow up. The analysis of observations made revealed SMR of inferior turbinate to be a very effective modality tor relieving nasal obstruction due to bony turbinal hypertrophy. The procedure has least interference with nasal mucosal integrity and functions and complications associated with the procedure have been found to be minimal. Histopathological examination of mucosa and of ostenid tissue revealed infiltration by chronic inflammatory cells suggesting chronic nonspecific inflammation either due to non-specific infections and / or allergy).

Non-randomized comparison of surgical modalities for paranasal sinus mycoses with intracranial extension.

Mycotic infections of paranasal sinuses are frequently reported in southern Asia. Aspergillus and Mucor species are the predominant ones. Intracranial extension of paranasal sinus mycoses is a difficult problem to manage. We report 18 cases of paranasal sinus mycoses with intracranial extensions. The commonest manifestations were nasal discharge (67%), nasal obstruction (50%), ocular symptoms such as proptosis (44%), telecanthus (39%) and ophthalmoplegia. Computerized tomography scans were found to be quite informative regarding the nature and extent of the disease (100% sensitivity and 78% specificity). A combined intracranial-extracranial approach (six cases) gave a distinct advantage over only adopting an extracranial approach (12 cases). A 17% incidence of CSF leak was noted by adopting only an extracranial approach as well as a recurrence in four cases out of the 12 that were treated using this method (P < 0.05). A slight increase in morbidity was associated with the combined intracranial-extracranial treatment, but no recurrence or significant complications were noted in this approach.