Watt-class CMOS-compatible power amplifier

Power amplifier is becoming a critical component for integrated photonics as the integrated devices try to carve out a niche in the world of real-world applications of photonics. That is because the signal generated from an integrated device severely lacks in power which is due mainly to the small size which, although gives size and weight advantage, limits the energy storage capacity of an integrated device due to the small volume, causing it to rely on its bench-top counterpart for signal amplification downstream. Therefore, an integrated high-power signal booster can play a major role by replacing these large solid-state and fiber-based benchtop systems. For decades, large mode area (LMA) technology has played a disruptive role by increasing the signal power and energy by orders of magnitude in the fiber-based lasers and amplifiers. Thanks to the capability of LMA fiber to support significantly larger optical modes the energy storage and handling capability has significantly increased. Such an LMA device on an integrated platform can play an important role for high power applications. In this work, we demonstrate LMA waveguide based CMOS compatible watt-class power amplifier with an on-chip output power reaching ~ 1W within a footprint of ~4mm2.The power achieved is comparable and even surpasses many fiber-based amplifiers. We believe this work opens up opportunities for integrated photonics to find real world application on-par with its benchtop counterpart

Towards On-Chip Ultrafast Pulse Amplification

Amplification of ultrafast optical signals is key to a large number of applications in photonics. While ultashort pulse amplification is well established in optical gain fibers, it is challenging to achieve in photonic-chip integrated waveguides. Recently, several integrated (quasi-)continuous-wave amplifiers have been demonstrated, based on rare-earth, heterogeneous semiconductor integration or nonlinear parametric gain [1]–[4]. On-chip amplification of ultrafast pulses, however, remains challenging due to the inherently small mode area and high-optical nonlinearity in integrated waveguides

Silicon photonics-based high-energy passively Q-switched laser

Chip-scale, high-energy optical pulse generation is becoming increasingly important as integrated optics expands into space and medical applications where miniaturization is needed. Q-switching of the laser cavity was historically the first technique to generate high-energy pulses, and typically such systems are in the realm of large bench-top solid-state lasers and fibre lasers, especially in the long wavelength range &gt;1.8 µm, thanks to their large energy storage capacity. However, in integrated photonics, the very property of tight mode confinement that enables a small form factor becomes an impediment to high-energy applications owing to small optical mode cross-sections. Here we demonstrate a high-energy silicon photonics-based passively Q-switched laser with a compact footprint using a rare-earth gain-based large-mode-area waveguide. We demonstrate high on-chip output pulse energies of &gt;150 nJ and 250 ns pulse duration in a single transverse fundamental mode in the retina-safe spectral region (1.9 µm), with a slope efficiency of ~40% in a footprint of ~9 mm2. The high-energy pulse generation demonstrated in this work is comparable to or in many cases exceeds that of Q-switched fibre lasers. This bodes well for field applications in medicine and space.</p

Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique

<p>Abstract</p> <p>Background</p> <p>In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the <it>Plasmodium falciparum </it>genes <it>Pfdhfr, Pfdhps </it>and <it>Pfcrt </it>before and a year after the introduction of SP.</p> <p>Methods</p> <p>Samples were collected during two cross sectional surveys in early 2002 and 2003 involving 796 and 692 children one year or older and adults randomly selected living in Maciana, an area located in Manhiça district, Southern Mozambique. Out of these, 171 and 173 <it>P. falciparum </it>positive samples were randomly selected to measure the frequency of resistance- related haplotypes in <it>Pfdhfr, Pfdhps </it>and <it>Pfcrt </it>based on results obtained by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA.</p> <p>Results</p> <p>The frequency of the SP-resistance associated <it>Pfdhps </it>double mutant (SGEAA) haplotype increased significantly from 14% to 35% (P < 0.001), while the triple mutant <it>Pfdhfr </it>haplotype (CIRNI) remained high and only changed marginally from 46% to 53% (P = 0.405) after one year with SP as first-line treatment in the study area. Conversely, the combined <it>Pfdhfr/Pfdhps </it>quintuple mutant haplotype increased from 8% to 26% (P = 0.005). The frequency of the chloroquine resistance associated <it>Pfcrt</it>-CVIET haplotype was above 90% in both years.</p> <p>Conclusion</p> <p>These retrospective findings add to the general concern on the lifespan of the combination of SP/artesunate in Mozambique. The high frequency of quintuple <it>Pfdhfr</it>/<it>Pfdhps </it>haplotypes found here as early as 2002 most likely cause ideal conditions for the development of artesunate tolerance in the <it>P. falciparum </it>populations and may even endanger the sensitivity to the second-line drug, Coartem^®.</p

Mental health in Europe during the COVID-19 pandemic: a systematic review

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions

Mental health in Europe during the COVID-19 pandemic: a systematic review

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions

Reconstruction of ancient microbial genomes from the human gut

Loss of gut microbial diversity in industrial populations is associated with chronic diseases, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000–2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces

Tamoxifen for the treatment of myeloproliferative neoplasms: a phase II clinical trial and exploratory analysis

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen’s safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study’s A’herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy