Raman Spectroscopy Using a Monolithic Spatial Heterodyne Raman Spectrometer for Planetary Exploration

Raman spectroscopy is a vibrational technique that provides detailed molecular and structural information for organic and inorganic molecules and minerals, and is uniquely suited for spacecraft applications, in the search for chemical indicators of life. This is why NASA sent two Raman spectrometers to Mars on the Mars 2020 Perseverance rover, as part of the SuperCam and SHERLOC instruments. The Raman spectrometers on Perseverance are conventional dispersive instruments that have been engineered to survive the harsh conditions of spaceflight. Future missions could benefit from smaller, more robust designs, especially missions to the Jovian planets, Jupiter and Saturn, their moons, asteroids and comets. The spatial heterodyne Raman spectrometer (SHRS) is one such spectrometer that has the potential to fit these needs. The SHRS is a Fourier transform interferometer with no moving parts that is capable of high spectral resolution, large spectral range, and very high light throughput as compared to dispersive slit-based spectrometers. And its design is compatible with monolithic construction techniques. This work describes a monolithic spatial heterodyne Raman spectrometer (mSHRS), where the optical components of the spectrometer are bonded to make a small, stable, one-piece structure. The mSHRS is very compact, measuring about 3.5 x 2.5 x 2.5 cm in size and weighing about 80 g. When compared to previously described free standing SHRS, the mSHRS was found to be more stable, have higher SNR, a large spectral range, and higher spectral resolution, and provided high SNR using CMOS camera detectors. The small size and high light throughput of the mSHRS makes it suitable for use with small platforms such as commercial drones, using the drone’s CMOS cameras as the detector. In drone studies, we found the performance of the mSHRS to be comparable to lab bench top measurements and the wide field of view of the mSHRS allowed measurements without the use of any collection optics, other than the drone camera lens. For some drone tests, an optical fiber was used to deliver the laser light to the sample, also possible because of the large field of view of the mSHRS

Effect of umbilical cord essential and toxic elements, thyroid levels, and Vitamin D on childhood development

Introduction: The in-utero environment has dramatic effects on childhood development. We hypothesized prenatal levels of inorganic agents, thyroid levels, and Vitamin D effect childhood development. Methods: Umbilical cord blood was collected from April 3, 2013 to January 30, 2014 and analyzed for 20 different elements, thyroid and Vitamin D. A retrospective review (n = 60) was performed of well-child examinations from birth to 5 years old (y.o.). Results: There were associations with calcium and 4 month BMI (p = \u3c0.01), 12 month language (p = 0.03); Magnesium and 6 month language (p = 0.04) and gross motor skills at 5 years old (y.o.) (p = 0.03); Copper and 12 month fine motor (p = 0.02); Zinc with fine motor (p = \u3c0.01) and language (p = 0.03) at 2 y.o.; Manganese was associated with language development at 2 y.o. (p = 0.02); Molybdenum and fine motor at 12 months of age (p = 0.02); Selenium with gross motor (p = 0.04) and BMI (p = 0.02) at 5 y.o.; Lead with cognitive function at 4 months (p = 0.04) and 2 y.o. (p = 0.01); Mercury with gross motor at 4 months (p = 0.04) and language at 2 y.o. (p = 0.02). Platinum at 12 months of age (p = \u3c.01) as well as multiple associations at 5 y.o. (p = \u3c.01). Thyroid function tests for free T3 were associated with multiple cognitive and physical milestones. T3 Uptake was associated with 5 y.o. gross motor skills (p = 0.02). Total and Free T4 was associated with cognitive development (p = \u3c.01) and fine motor development, respectively. Vitamin D was associated with a delay of fine motor development (p\u3c0.01). Conclusion: There were multiple associations between umbilical cord essential and toxic elements, thyroid levels, and Vitamin D on childhood development

A High Pressure Time Projection Chamber with Optical Readout

Measurements of proton-nucleus scattering and high resolution neutrino-nucleus interaction imaging are key to reduce neutrino oscillation systematic uncertainties in future experiments. A High Pressure Time Projection Chamber (HPTPC) prototype has been constructed and operated at Royal Holloway University of London and CERN as a first step in the development of a HPTPC capable of performing these measurements as part of a future long-baseline neutrino oscillation experiment such as the Deep Underground Neutrino Experiment. In this paper we describe the design and operation of the prototype HPTPC with an argon based gas mixture. We report on the successful hybrid charge and optical readout, using four CCD cameras, of signals from Am-241 sources.Comment: 40 pages, 24 figure

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Neutrino oscillation parameters from [nu]e appearance in the T2K experiment

The T2K Experiment is a long-baseline accelerator neutrino oscillation experiment, whose primary aim is to look for νe appearance in a νμ beam. A predominantly νμ beam is produced at J-PARC in Tokai on the east coast of Japan, and neutrino interactions are measured both by a near detector complex, 280 m from the neutrino production target,and by a large water Cerenkov detector, Super-Kamiokande, 295 km away. This thesis is concerned with oscillations νμ → νe, within both a standard three neutrino model and a model in which there is one additional sterile neutrino. By looking at νe appearance over the T2K baseline, this thesis looks for oscil- lations involving one additional sterile neutrino. A region of the short baseline neutrino oscillation parameter space favoured by other experiments is excluded at 3σ. The ND280 is also used to search for νe appearance over a short baseline. A νe selection is developed, and limits on the short baseline oscillation parameter space are set. Sensitivity predictions are also made for future T2K running. The T2K ND280 is interesting for this work since the detector technology is different to that of other experiments that have seen indications of short baseline electron-neutrino appearance. In the standard three-flavour neutrino oscillation picture, a combined analy- sis of the electron-neutrino appearance results of T2K and another long-baseline accelerator neutrino experiment, MINOS, is presented. Combining the two re- sults with the Feldman-Cousins method results in sin2 2θ13 = 0 being excluded at 2.7σ, assuming the normal neutrino mass hierarchy.</p