Infrared Non-detection of Fomalhaut b -- Implications for the Planet Interpretation

The nearby A4-type star Fomalhaut hosts a debris belt in the form of an eccentric ring, which is thought to be caused by dynamical influence from a giant planet companion. In 2008, a detection of a point-source inside the inner edge of the ring was reported and was interpreted as a direct image of the planet, named Fomalhaut b. The detection was made at ~600--800 nm, but no corresponding signatures were found in the near-infrared range, where the bulk emission of such a planet should be expected. Here we present deep observations of Fomalhaut with Spitzer/IRAC at 4.5 um, using a novel PSF subtraction technique based on ADI and LOCI, in order to substantially improve the Spitzer contrast at small separations. The results provide more than an order of magnitude improvement in the upper flux limit of Fomalhaut b and exclude the possibility that any flux from a giant planet surface contributes to the observed flux at visible wavelengths. This renders any direct connection between the observed light source and the dynamically inferred giant planet highly unlikely. We discuss several possible interpretations of the total body of observations of the Fomalhaut system, and find that the interpretation that best matches the available data for the observed source is scattered light from transient or semi-transient dust cloud.Comment: 12 pages, 4 figures, ApJ 747, 166. V2: updated acknowledgments and reference

Reduction of Coincident Photomultiplier Noise Relevant to Astroparticle Physics Experiment

In low background and low threshold particle astrophysics experiments using observation of Cherenkov or scintillation light it is common to use pairs or arrays of photomultipliers operated in coincidence. In such circumstances, for instance in dark matter and neutrino experiments, unexpected PMT noise events have been observed, probably arising from generation of light from one PMT being detected by one or more other PMTs. We describe here experimental investigation of such coincident noise events and development of new techniques to remove them using novel pulse shape discrimination procedures. When applied to data from a low background NaI detector with facing PMTs the new procedures are found to improve noise rejection by a factor of 20 over conventional techniques, with significantly reduced loss of signal events.Comment: Submitted to NIM

Objective Assessment and Design Improvement of a Staring, Sparse Transducer Array by the Spatial Crosstalk Matrix for 3D Photoacoustic Tomography.

Accurate reconstruction of 3D photoacoustic (PA) images requires detection of photoacoustic signals from many angles. Several groups have adopted staring ultrasound arrays, but assessment of array performance has been limited. We previously reported on a method to calibrate a 3D PA tomography (PAT) staring array system and analyze system performance using singular value decomposition (SVD). The developed SVD metric, however, was impractical for large system matrices, which are typical of 3D PAT problems. The present study consisted of two main objectives. The first objective aimed to introduce the crosstalk matrix concept to the field of PAT for system design. Figures-of-merit utilized in this study were root mean square error, peak signal-to-noise ratio, mean absolute error, and a three dimensional structural similarity index, which were derived between the normalized spatial crosstalk matrix and the identity matrix. The applicability of this approach for 3D PAT was validated by observing the response of the figures-of-merit in relation to well-understood PAT sampling characteristics (i.e. spatial and temporal sampling rate). The second objective aimed to utilize the figures-of-merit to characterize and improve the performance of a near-spherical staring array design. Transducer arrangement, array radius, and array angular coverage were the design parameters examined. We observed that the performance of a 129-element staring transducer array for 3D PAT could be improved by selection of optimal values of the design parameters. The results suggested that this formulation could be used to objectively characterize 3D PAT system performance and would enable the development of efficient strategies for system design optimization

Strategic Alliances for Technology Adoption: Alliances and Partnerships for Blockchain Adoption

This paper aims to study the relevance and importance of strategic alliances for emerging technology adoption. The case researched and discussed here is Blockchain adoption in the semiconductor industry. As a technology, Blockchain has been around for over a decade and is known to provide tremendous value in business transactions. However, the adoption has not gained traction mainly due to the fact that it takes a network to adopt an industrial Blockchain and cannot work in silos. Most companies are shying away from it as they haven\u27t explored what makes a successful strategy for adoption. A literature review was done on the similar technology adoption in the past. The nature of Blockchain and its network dependency were considered. It was clear that strategic alliances are the way to move forward. The various aspects to be considered while forming an alliance, such as understanding the core competencies, finding the right partners, and form of alliances was studied. The research converged in understanding the fact that companies should move away from the transactional business model and have the right expectations and scoping on all sides, standardization, digital integration, and a steady focus on security and privacy

Tumor Recurrence Incidence Following Hand-Assisted Laparoscopic Nephroureterectomy

BACKGROUND AND OBJECTIVES: We evaluated the incidence of tumor recurrence following hand-assisted laparoscopic nephroureterectomy (HALNU) for the treatment of upper tract urothelial carcinoma. METHODS: The medical records of consecutive patients who underwent HALNU by a single surgeon (CW) between October 2001 and May 2005 were reviewed. The ureter was clipped before kidney dissection to prevent distal migration of tumor. Following liberation of the kidney, the bladder cuff and intramural ureter were excised by using a Collings knife under cystoscopic guidance. RESULTS: Ten patients were identified. The primary location of disease was confined to the intrarenal collecting system. Eight high-grade (HG) and 2 low-grade (LG) tumors were removed, with pT3 (6), pT2 (1), pT1 (1), and pTa (2) disease. The patient having a LG pTa urothelial carcinoma developed pulmonary metastasis 20 months following surgery and survived an additional 26 months. Two patients, each having a HG pT3 tumor, developed a urothelial carcinoma in the bladder contralateral to the site of ureteral excision. At a mean follow-up of 41 months, there has been no evidence of tumor recurrence in the pelvis. CONCLUSION: Our technique of HALNU does not appear to harbor an increased risk for urothelial carcinoma recurrence

A systematic review of non-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva. AIM/HYPOTHESIS: We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments. METHODS: We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. RESULTS: 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms. CONCLUSIONS: Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs. PROPSERO REGISTRATION: CRD42020223648. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10651-1

A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis

Background: Up to 50% of people with amyotrophic lateral sclerosis (ALS) experience cognitive dysfunction, whilst depression and anxiety are reported in up to 44% and 33%, respectively. These symptoms impact on quality of life, and are associated with a poorer prognosis. Historically, outcomes in clinical trials have focused on the effect of candidate drugs on physical functioning.Methods: We reviewed the past 25 years of clinical trials of investigative medicinal products in people with ALS, since the licensing of riluzole, and extracted data on frequency and type of assessment for neuropsychiatric symptoms and cognitive impairment. Trial registry databases, including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed, were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 31/10/2019. No language restrictions were applied. Outcome measures, exclusion criteria and assessment tool used were extracted.Results: 216 trials, investigating 26,326 people with ALS, were reviewed. 35% assessed neuropsychiatric symptoms, and 22% assessed cognition, as Exclusion Criteria or Outcome Measures. 3% (n = 6) of trials assessed neuropsychiatric symptoms as a Secondary Outcome Measure, and 4% (n = 8) assessed cognition as Outcome Measures; only one trial included assessments for both cognition and neuropsychiatric symptoms as Outcome Measures. Three ALS-specific assessments were used in six trials.Conclusions: Trials for people with ALS have neglected the importance of neuropsychiatric symptoms and cognitive impairment. Evaluation of these extra-motor features is essential to understanding the impact of candidate drugs on all symptoms of ALS.</p

Screening and identification of differentially expressed transcripts in circulating cells of prostate cancer patients using suppression subtractive hybridization

BACKGROUND: Tumor metastasis and changes in host immunosurveillance are important components in cancer development. Tumor cell invasion into the bloodstream is an essential step for systemic metastasis. Currently, the detection of tumor cells in the circulation is mainly dependent upon the utilization of known epithelial cell markers. However, expression of these molecules is not limited to cancer patients; healthy people also have a small number of epithelial cells in their circulation. Utilizing these markers to detect circulating tumor cells (CTCs) cannot adequately explain the mechanisms of tumor cell survival or their development of metastatic potential in peripheral blood. The immune system can also evolve along with the cancer, actually promoting or selecting the outgrowth of tumor variants. Unfortunately, both metastasis and immunosurveillance remain mysterious and are debatable because we have yet to define the molecules that participate in these processes. We are interested in identifying the existence of expressed genes, or mRNA species, that are specifically associated with circulating cells of cancer-bearing patients using prostate cancer (PCa) as a model. RESULTS: We established two comprehensive subtracted cDNA libraries using a molecular technique called suppression subtractive hybridization. This technique selectively amplifies transcripts that are specifically expressed in circulating cells of either PCa patients or healthy men. Following sequencing reaction, we showed that 17 out of 23 (73.9%) sequenced clones did not match any mRNAs in the GenBank database. This result suggests that genes associated with alterations in circulating cells of cancer-bearing patients are largely unknown. Semi-quantitative RT-PCR confirmed that two genes are up-regulated in circulating cells of PCa patients, whereas another two genes are down-regulated in the same patients. CONCLUSION: The comprehensive gene expression analysis is capable of identifying differentially expressed genes in circulating cells of healthy men and PCa patients. We did not attempt to enrich specific cell types in this study because phenotypes of CTCs and subsets of leukocytes participating in immunosurveillance remain largely unknown. Continuous studies of these differentially expressed genes will eventually lead us to understand the mechanisms involved in tumor metastasis and immune modulation during cancer development