Lysosomal Acid Lipase Deficiency: Therapeutic Options

Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency. Diagnosis is based on demonstration of decreased LAL enzyme activity, complemented by analysis of the cognate gene defects. Therapeutic options include dietary manipulation and the use of lipid-lowering drugs. Sebelipase alfa, a recombinant enzyme replacement therapy, has garnered regulatory approval, following demonstration of improvements in disease-relevant markers and clinical benefit in clinical trials, which included increased survival in the most severe cases

The Role of Welsh Language Journalism in Shaping the Construction of Welsh Identity and the National Character of Wales.

Ever since Edward I subjugated the Welsh in 1282 and, a little over 250 years later, Henry VIII attempted to wipe the country off the map, Wales has lived in the overpowering shadow of its powerful English neighbour. Unlike Scotland, Wales did not develop its own legal and banking systems and symbols of national identity were slow to appear. This thesis argues that, while many national institutions are relatively recent innovations, the Welsh language is the most potent symbol of national identity. More importantly, it argues that it was the journalists who used the language to communicate “Welshness”. They, in many ways, created a radical approach to politics, an antipathy towards the Established Church, an occasional suspicion of the country’s English neighbour, an interest in international affairs and an awareness of the rich cultural heritage of the country. This argument has been pursued by way of a critical survey of the development of Welsh-language journalism. To date, there are no specific studies on this subject - particularly relatively recent developments since the advent of S4C in 1982. Indeed, little scholarly attention has been paid to the fast-developing world of on-line journalism and the use of social media as far as the Welsh language is concerned. The main analytical focus of this thesis is to examine the impact of Welsh-language journalism on the national consciousness in Wales. This has been done through a series of case studies, content analyses and interviews with influential and experienced journalists and editors in all fields of journalism, namely print, broadcast and on-line. The conclusion is that journalists reintroduced the Welsh people to their literature and poetry, they wrote about traditional music, they adopted a radical approach to national and international politics, they were sympathetic to the non-conformist religion of the majority of people and news was reported from a Welsh point of view. Indeed, the phrase Welsh Renaissance has been applied to the section of this thesis related to Early Periodicals. There is considerable scope for further research. There is no history of solely Welsh-language journalism in a single volume. In recent years, journalism has moved on rapidly, as new forms of journalism have rapidly become established. There is little analysis of the effects of these outlets on Welsh consumers, let alone the effects of radio and television to any great degree. In addition, as Wales becomes more confident in the post-devolution era, Welsh journalism becomes more relevant and there is scope to chart how much influence Welsh-language journalism really has on its consumers

Tunable cavity coupling of the zero phonon line of a nitrogen-vacancy defect in diamond

We demonstrate the tunable enhancement of the zero phonon line of a single nitrogen-vacancy color center in diamond at cryogenic temperature. An open cavity fabricated using focused ion beam milling provides mode volumes as small as 1.24 $\mu$m$^3$. In-situ tuning of the cavity resonance is achieved with piezoelectric actuators. At optimal coupling of the full open cavity the signal from individual zero phonon line transitions is enhanced by about a factor of 10 and the overall emission rate of the NV$^-$ center is increased by 40% compared with that measured from the same center in the absence of cavity field confinement. This result is important for the realization of efficient spin-photon interfaces and scalable quantum computing using optically addressable solid state spin qubits.Comment: 11 pages Main Article + 4 pages Supplementary Info Typos fixed from v

Improving the kinetic couplings in lattice nonrelativistic QCD

We improve the non-relativistic QCD (NRQCD) action by comparing the dispersion relation to that of the continuum through $\mathcal{O}(p^6)$ in perturbation theory. The one-loop matching coefficients of the $\mathcal{O}(p^4)$ kinetic operators are determined, as well as the scale at which to evaluate $\alpha_s$ in the $V$-scheme for each quantity. We utilise automated lattice perturbation theory using twisted boundary conditions as an infrared regulator. The one-loop radiative corrections to the mass renormalisation, zero-point energy and overall energy-shift of an NRQCD $b$-quark are also found. We also explore how a Fat$3$-smeared NRQCD action and changes of the stability parameter $n$ affect the coefficients. Finally, we use gluon field ensembles at multiple lattice spacing values, all of which include $u$, $d$, $s$ and $c$ quark vacuum polarisation, to test how the improvements affect the non-perturbatively determined $\Upsilon(1S)$ and $\eta_b(1S)$ kinetic masses, and the tuning of the $b$ quark mass

A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure

Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse

Feasibility and Coverage of Implementing Intermittent Preventive Treatment of Malaria in Pregnant women Contacting Private or Public Clinics in Tanzania: Experience-based Viewpoints of Health Managers in Mkuranga and Mufindi districts.

Evidence on healthcare managers' experience on operational feasibility of malaria intermittent preventive treatment for malaria during pregnancy (IPTp) using sulphadoxine-pyrimethamine (SP) in Africa is systematically inadequate. This paper elucidates the perspectives of District Council Health Management Team (CHMT)s regarding the feasibility of IPTp with SP strategy, including its acceptability and ability of district health care systems to cope with the contemporary and potential challenges. The study was conducted in Mkuranga and Mufindi districts. Data were collected between November 2005 and December 2007, involving focus group discussion (FGD) with Mufindi CHMT and in-depth interviews were conducted with few CHMT members in Mkuranga where it was difficult to summon all members for FGD. Participants in both districts acknowledged the IPTp strategy, considering the seriousness of malaria in pregnancy problem; government allocation of funds to support healthcare staff training programmes in focused antenatal care (fANC) issues, procuring essential drugs distributed to districts, staff remuneration, distribution of fANC guidelines, and administrative activities performed by CHMTs. The identified weaknesses include late arrival of funds from central level weakening CHMT's performance in health supervision, organising outreach clinics, distributing essential supplies, and delivery of IPTp services. Participants anticipated the public losing confidence in SP for IPTp after government announced artemither-lumefantrine (ALu) as the new first-line drug for uncomplicated malaria replacing SP. Role of private healthcare staff in IPTp services was acknowledged cautiously because CHMTs rarely supplied private clinics with SP for free delivery in fear that clients would be required to pay for the SP contrary to government policy. In Mufindi, the District Council showed a strong political support by supplementing ANC clinics with bottled water; in Mkuranga such support was not experienced. A combination of health facility understaffing, water scarcity and staff non-adherence to directly observed therapy instructions forced healthcare staff to allow clients to take SP at home. Need for investigating in improving adherence to IPTp administration was emphasised. High acceptability of the IPTp strategy at district level is meaningless unless necessary support is assured in terms of number, skills and motivation of caregivers and availability of essential supplies

PENGARUH LAMA PERENDAMAN DALAM LARUTAN BUBUR BLACK MULBERRY (Morus nigra) DAN SUHU PENGERINGAN TERHADAP KARAKTERISTIK BERAS IR 64

PT. Electric Wire Indonesia atau lebih dikenal dengan PT. EWINDO (persero) merupakan perusahaan yang bergerak di bidang manufaktur dengan produk yang dihasilkan, yaitu Kabel Elektrik & Kabel Otomotif, Power Supply Cord, dan Kawat Pengaman. Saat ini PT. EWINDO sedang menghadapi permasalahan kualitas. Kegagalan terhadap fungsi terlihat pada saat uji fungsional tes produk power supply cord. Saat ini perbaikan yang dilakukan perusahaan hanya melakukan perbaikan ulang produk dan pemeriksaan ditahap manufakturing, tanpa mengetahui faktor-faktor yang berpengaruh terhadap kegagalan suatu produk sehingga dikemudian hari dapat terulang kembali kegagalan yang sama. Oleh sebab itu, diperlukan suatu rencana perbaikan berkelanjutan. Jenis kegagalan fungsional pada power supply cord terjadi akibat beberapa modus kegagalan proses sehingga dilakukan perbaikan proses dengan merancang ulang proses. Perlu diketahui faktor prioritas perbaikan terhadap kegagalan proses dengan menggunakan analisis FMEA (Failure Mode and Effect Analysis) untuk menghilangkan potensial kegagalan. Didalam melakukan perbaikan kualitas, dilihat dari perhitungan nilai RPN (Risk Priority Number). Nilai RPN didasarkan kepada faktor severity, occurance, detection. Diketahui nilai RPN Wall thickness sebesar 360, Injection rate 280, kerapihan hasil crimping 160, holding pressure 140, stripper 120. Rancangan ulang proses produksi dapat mengurangi nilai RPN dari setiap modus kegagalan berupa penambahan proses pembersihan cavity, penambahan waktu untuk injection rate, pembersihan selang hidrolik, penambahan waktu tahan pada holding pressure, penggantian pegas untuk stripper. Perbaikan menghasilkan nilai estimasi berdasarkan pendapat para ahli. Perbaikan secara berkelanjutan dilakukan dengan melihat faktor mana saja yang belum diteliti. Kata kunci : Quality Improvement, Failure Mode and Effect Analysis (FMEA), prinsip 5W+1H, reliabilit

Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing and multi-potent in vitro and in vivo.

European Research Council, European Community 7th Framework project ENDOSTEM (contract number FP7-Health-2009-ENDOSTEM 241440 (Activation of vasculature-associated stem cells and muscle stem cells for the repair and maintenance of muscle tissue)

Modelling the potential non-breeding distribution of Spoon-billed Sandpiper Calidris pygmaea

SummaryThe Spoon-billed Sandpiper Calidris pygmaea is a ‘Critically Endangered’ migratory shorebird. The species faces an array of threats in its non-breeding range, making conservation intervention essential. However, conservation efforts are reliant on identifying the species’ key stopover and wintering sites. Using Maximum Entropy models, we predicted Spoon-billed Sandpiper distribution across the non-breeding range, using data from recent field surveys and satellite tracking. Model outputs suggest only a limited number of stopover sites are suitable for migrating birds, with sites in the Yellow Sea and on the Jiangsu coast in China highlighted as particularly important. All the previously known core wintering sites were identified by the model including the Ganges-Brahmaputra Delta, Nan Thar Island and the Gulf of Mottama. In addition, the model highlighted sites subsequently found to be occupied, and pinpointed potential new sites meriting investigation, notably on Borneo and Sulawesi, and in parts of India and the Philippines. A comparison between the areas identified as most likely to be occupied and protected areas showed that very few locations are covered by conservation designations. Known sites must be managed for conservation as a priority, and potential new sites should be surveyed as soon as is feasible to assess occupancy status. Site protection should take place in concert with conservation interventions including habitat management, discouraging hunting, and fostering alternative livelihoods.Field surveys in Russian non-breeding grounds were supported by RSPB, MHS and NABU. Field surveys in Gulf of Mottama partly supported by BBC Wildlife Fund. Satellite tagging data collection partly supported by The Biodiversity Investigation, Observation and Assessment Program (2019 - 2023) of the Ministry of Ecology and Environment of China, RSPB and a private donor. Bangladesh Spoon-billed Sandpiper Conservation Project’s fieldwork in Meghna Estuary (2015 - 2016) supported by RSPB. Data collection by EL partly supported by Basic research program (budgetary funds), projects number АААА-А19-119022190168-8 and АААА-А19-119021990093-8). PT supported by Moscow State University Grant for Leading Scientific Schools "Depository of the Living Systems" in the MSU Development Program framework. TBL was funded by the Natural Environment Research Council UK, and the IAPETUS Doctoral Training Partnership