Switching and generation of ultrashort pulses using all-fibre devices

Serial and parallel interconnection of photonic devices is integral to the construction of any all-optical data processing system. This thesis presents results from a series of experiments centering on the use of the nonlinear-optical loop mirror (NOLM) switch in architectures for the manipulation and generation of ultrashort pulses. Detailed analysis of soliton switching in a single NOLM and cascade of two NOLM's is performed, centering on primary limitations to device operation, effect of cascading on amplitude response, and impact of switching on the characteristics of incident pulses. By using relatively long input pulses, device failure due to stimulated Raman generation is postponed to demonstrate multiple-peaked switching for the first time. It is found that while cascading leads to a sharpening of the overall switching characteristic, pulse spectral and temporal integrity is not significantly degraded, and emerging pulses retain their essential soliton character. In addition, by including an asymmetrically placed in-fibre Bragg reflector as a wavelength selective loss element in the basic NOLM configuration, both soliton self-switching and dual-wavelength control-pulse switching are spectrally quantised. Results are presented from a novel dual-wavelength laser configuration generating pulse trains with an ultra-low rms inter-pulse-stream timing jitter level of 630fs enabling application in ultrafast switching environments at data rates as high as 130GBits/s. In addition, the fibre NOLM is included in architectures for all-optical memory, demonstrating storage and logical inversion of a 0.5kByte random data sequence; and ultrafast phase-locking of a gain-switched distributed feedback laser at 1.062GHz, the fourteenth harmonic of the system baseband frequency. The stringent requirements for environmental robustness of these architectures highlight the primary weaknesses of the NOLM in its fibre form and recommendations to overcome its inherent drawbacks are presented

Strongyloidiasis in personnel of the Regional Assistance Mission to Solomon Islands (RAMSI)

Objective: to investigate the first reported cases of strongyloidiasis in the Solomon Islands, and to establish whether this disease poses a risk to personnel of the Regional Assistance Mission to Solomon Islands (RAMSI). Design, setting and participants: Retrospective review of the pathology database of the RAMSI Medical Facility in Honiara, Solomon Islands, for the period 1 July 2006 – 30 September 2007. Main outcome measures: number and clinical features of confirmed cases of Strongyloides stercoralis infestation, as diagnosed by serological tests or faecal microscopy. Results: fourteen confirmed cases of strongyloidiasis in previously healthy RAMSI participants were identified. Of 13 patients with notes available, symptoms documented at presentation included epigastric pain (10 patients), diarrhoea (7) and urticaria (4). Clinical disease in all patients responded to oral antihelminthic therapy (albendazole or ivermectin). Conclusions: Strongyloidiasis is endemic in the Solomon Islands and a risk for RAMSI personnel. Australian medical professionals should be aware of this potentially fatal and lifelong infestation, particularly the importance of an occupation history, appropriate diagnostic tests, effective treatment and adequate follow-up to document cure. We recommend implementation of a postdeployment screening program for strongyloidiasis

Risk of metastatic disease using [F-18]PSMA-1007 PET/CT for primary prostate cancer staging

Background Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [Ga-68]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [F-18]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [F-18]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. Results The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease. Conclusion Metastatic disease according to [F-18]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [F-18]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax

Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons.

Enteroendocrine cells are specialised sensory cells located in the intestinal epithelium and generate signals in response to food ingestion. Whilst traditionally considered hormone-producing cells, there is evidence that they also initiate activity in the afferent vagus nerve and thereby signal directly to the brainstem. We investigate whether enteroendocrine L-cells, well known for their production of the incretin hormone glucagon-like peptide-1 (GLP-1), also release other neuro-transmitters/modulators. We demonstrate regulated ATP release by ATP measurements in cell supernatants and by using sniffer patches that generate electrical currents upon ATP exposure. Employing purinergic receptor antagonists, we demonstrate that evoked ATP release from L-cells triggers electrical responses in neighbouring enterocytes through P2Y2 and nodose ganglion neurones in co-cultures through P2X2/3-receptors. We conclude that L-cells co-secrete ATP together with GLP-1 and PYY, and that ATP acts as an additional signal triggering vagal activation and potentially synergising with the actions of locally elevated peptide hormone concentrations.Wellcome Trust joint investigator award (106262/Z/14/Z and 106263/Z/14/Z); MRC programme within the Metabolic Diseases Unit (MRC_MC_UU_12012/3); MRC Metabolic Diseases Unit [MRC_MC_UU_12012/5] ; Wellcome Trust Strategic Award [100574/Z/12/Z

Towards controlling the solid state valence tautomeric interconversion character by solvation

Crystals of [Co<i>(diox)</i>₂­(4-NO₂-py)₂] (<b>1</b>) and [Co<i>(diox)</i>₂­(4-CN-py)₂] (<b>2</b>) where <i>diox</i> are the <i>o</i>-dioxolene 3,5-di-<i>t</i>-butylsemiquinonate (SQ^•–) and/or 3,5-di-<i>t</i>-butylcatecholate (Cat^2–) ions, 4-NO₂-py is 4-nitro-pyridine, 4-CN-py is 4-cyano-pyridine, are among the few known crystals presenting both thermally induced and photoinduced <i>ls</i>-[M⁺³(SQ^•–)­(Cat^2–)] ↔ <i>hs</i>-[M²⁺(SQ^•–)₂] valence tautomeric interconversion (VTI). In <b>2</b>, the thermal-induced VTI is cooperative, characterizing an abrupt conversion, and in <b>1</b> it is noncooperative. In this work, crystals of [Co<i>(diox)</i>₂­(4-NO₂-py)₂]­·benzene (<b>1BZ</b>), [Co<i>(diox)</i>₂­(4-NO₂-py)₂]­·toluene (<b>1TL</b>), [Co<i>(diox)</i>₂­(4-CN-py)₂]­·benzene (<b>2BZ</b>), and [Co<i>(diox)</i>₂­(4-CN-py)₂]­·toluene (<b>2TL</b>) have been prepared and analyzed by single crystal X-ray diffraction in order to investigate how solvation modulates thermally induced VTI. Crystallographic data were also successfully used together with the two-state equilibrium equation to estimate Δ<i>H</i>° and Δ<i>S</i>° VTI thermodynamic parameters. The solvate crystals, like the nonsolvated ones, present essentially reversible thermally induced VTI. The <b>1TL</b> crystal presents the same monoclinic symmetry and the same intermolecular hydrogen-bonded network of <b>1</b>, and both present a noncooperative thermal-induced VTI. The <b>1BZ</b> crystal has triclinic symmetry and presents a cooperative VTI with a thermal hysteresis of ∼30 K. In contrast to <b>2</b>, thermally induced VTI in <b>2BZ</b> and <b>2TL</b> is noncooperative despite the fact that <b>2</b>, <b>2BZ</b>, and <b>2TL</b> crystals exhibit the same monoclinic symmetry and the same intermolecular hydrogen-bonded network. In <b>2BZ</b> and <b>2TL</b> benzene and toluene molecules as well as the <i>t</i>-butyl groups of the <i>o</i>-dioxolene molecules convert gradually from being dynamically disordered at about 300 K to a static disorder state below 150 K. The layer separation distance of interacting [Co<i>(diox)</i>₂­(4-X-py)₂], X = CN and NO₂, molecules in all solvate crystals is ∼15 Å, whereas in <b>2</b>, which presents cooperative VTI, it is ∼12 Å. An order–disorder component might account for the stabilization of the metastable <i>hs</i>-Co²⁺ state in <b>2BZ</b> and in <b>2TL</b>, but no disorder was found in the <b>1TL</b> crystals. Therefore, the lack of cooperativity in the thermally induced VTI in these crystals seems to be due to the large distance between the layers of interacting molecules. Cooperativity in the VTI of <b>1BZ</b> crystal is likely to be related with the unique molecular bond scheme network that connects neighboring active [Co<i>(diox)</i>₂­(4-NO₂-py)₂] molecules through the <i>o</i>-dioxolene oxygen atoms bonded directly to the Co ion

Global economic costs of aquatic invasive alien species

Much research effort has been invested in understanding ecological impacts of invasive alien species (IAS) across ecosystems and taxonomic groups, but empirical studies about economic effects lack synthesis. Using a comprehensive global database, we determine patterns and trends in economic costs of aquatic IAS by examining: (i) the distribution of these costs across taxa, geographic regions and cost types; (ii) the temporal dynamics of global costs; and (iii) knowledge gaps, especially compared to terrestrial IAS. Based on the costs recorded from the existing literature, the global cost of aquatic IAS conservatively summed to US$345 billion, with the majority attributed to invertebrates (62$23 billion in 2020. Costs are likely considerably underrepresented compared to terrestrial IAS; only 5% of reported costs were from aquatic species, despite 26% of known invaders being aquatic. Additionally, only 1% of aquatic invasion costs were from marine species. Costs of aquatic IAS are thus substantial, but likely underreported. Costs have increased over time and are expected to continue rising with future invasions. We urge increased and improved cost reporting by managers, practitioners and researchers to reduce knowledge gaps. Few costs are proactive investments; increased management spending is urgently needed to prevent and limit current and future aquatic IAS damages. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit.

By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant KV6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (KV6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express KV2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing KV6.4-Met419, the voltage dependence of inactivation for KV2.1 is more depolarized compared with neurons overexpressing KV6.4. Finally, KV6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that KV6.4 can influence human labor pain by modulating the excitability of uterine nociceptors.MCL, DKM, DW, and CGW acknowledge funding from Addenbrooke’s Charitable Trust and the NIHR Cambridge Biomedical Research Centre. MN was funded by the Wellcome Trust (200183/Z/15/Z); JH and ESS by a Rosetrees Postdoctoral Grant (A1296) and the BBSRC (BB/R006210/1); GC and ESS by Versus Arthritis Grants (RG21973); VBL and FR by the Wellcome Trust (106262/Z/14/Z and 106263/Z/14/Z) and a joint MRC programme within the Metabolic Diseases Unit (MRC_MC_UU_12012/3). EF, GI and CB were funded by the Cambridge NIHR Biomedical Research Centre Integrative Genomics theme and LAP by a BBSRC-funded studentship (BB/M011194/1)

Twenty years online! A brief history of palaeontologia electronica

This issue marks the 20th anniversary of Palaeontologia Electronica (PE). From modest beginnings as a series of discussions on the PaleoNet listserver in 1996, it has become a well-recognised venue for publication and dissemination of research, techniques, and resources in palaeontology. The journal has many “firsts” to its credit, from the first species named on the internet, the first scientific journal with a plain-language abstract, and the first PDF “reprints” in palaeontology. Over 20 years PE also tried many new approaches that weren’t subsequently adopted by the broader scientific community, such as audio abstracts and animated journal covers. This anniversary issue gives us an opportunity to look back at the beginnings of the journal, its initial aims and aspirations, and to chronicle its evolution. It is as much a reflection of the changing nature of PE as it is a reminder of the larger scale changes that have taken place in the world of palaeontology, the internet, and our community over the past two decades

Self-testing for cancer: a community survey

<p>Abstract</p> <p>Background</p> <p>Cancer-related self-tests are currently available to buy in pharmacies or over the internet, including tests for faecal occult blood, PSA and haematuria. Self-tests have potential benefits (e.g. convenience) but there are also potential harms (e.g. delays in seeking treatment). The extent of cancer-related self-test use in the UK is not known. This study aimed to determine the prevalence of cancer-related self-test use.</p> <p>Methods</p> <p>Adults (n = 5,545) in the West Midlands were sent a questionnaire that collected socio-demographic information and data regarding previous and potential future use of 18 different self-tests. Prevalence rates were directly standardised to the England population. The postcode based Index of Multiple Deprivation 2004 was used as a proxy measure of deprivation.</p> <p>Results</p> <p>2,925 (54%) usable questionnaires were returned. 1.2% (95% CI 0.83% to 1.66%) of responders reported having used a cancer related self test kit and a further 36% reported that they would consider using one in the future. Logistic regression analyses suggest that increasing age, deprivation category and employment status were associated with cancer-related self-test kit use.</p> <p>Conclusion</p> <p>We conclude that one in 100 of the adult population have used a cancer-related self-test kit and over a third would consider using one in the future. Self-test kit use could alter perceptions of risk, cause psychological morbidity and impact on the demand for healthcare.</p