Search Results (16)

Narcolepsy Type 1 (NT1) is a rare chronic neurological disorder characterized by core clinical manifestations such as excessive daytime sleepiness (EDS), cataplexy, sleep paralysis (SP), hypnagogic and hypnopompic hallucinations (HHs), and disrupted nocturnal sleep (DNS). Patients often experience comorbidities, including cognitive impairment, psychiatric disorders, and metabolic syndrome, necessitating lifelong management. Current therapeutic approaches primarily involve pharmacologic treatments for symptomatic relief, supplemented by non-pharmacologic interventions aimed at alleviating EDS and cataplexy. However, existing therapies are limited in efficacy and do not offer a cure. In recent years, a deeper understanding of the central role played by the orexin (hypocretin) system in the pathogenesis of NT1 has led to breakthrough advances in mechanism-based therapies targeting this pathway. Notably, selective orexin-2 receptor (OX2R) agonists such as TAK-861 have shown remarkable efficacy in Phase II/III clinical trials, holding the potential to fundamentally reshape the NT1 treatment landscape. This review systematically outlines current treatment options for NT1, with a focus on management strategies for atypical symptoms and special populations. It also highlights emerging therapeutic directions—including orexin-targeted agents, immunotherapies, and orexin cell/gene treatments—along with their future development. Full article

Objectives: This study aims to evaluate the efficacy and safety of valproic acid (VPA) transition regimens (from intravenous to oral tablets) for anti-seizure treatment. Methods: A retrospective analysis was conducted on inpatients treated with intravenous VPA and oral tablets for epilepsy at the Sir Run Run Shaw Hospital, affiliated with Zhejiang University, between January 2022 and December 2023. Various transition strategies from VPA injections to tablets were examined, and the efficacy and safety of different transition strategies were analyzed. Results: A total of 164 inpatients receiving VPA transition therapy were included in this study, which was divided into three groups based on the transition timing: the 0 h group, the 0–48 h group, and the >48 h group. Regarding VPA dosage, the median daily dose of intravenous VPA was separately 1076.50 mg/day, 1200 mg/day and 1438 mg/day in the 0 h group, 0–48 h group, and the >48 h group. During transition, the daily doses of VPA were significantly higher than that before and after the transition. After completely switching to oral administration, they were all decreased to 1000 mg/day. Moreover, a significant difference regarding the clinical efficacy was observed among the three groups. The >48 h group showed the highest rate of clinical efficacy, which was significantly greater than that of the 0 h group and 0–48 h group. Although there was no statistical significance detected regarding the average blood serum concentrations among the three groups; notably, a higher proportion of patients in the >48 h group (19.35%) had blood concentrations exceeding the desired therapeutic window compared with the 0–48 h group (8.06%) and 0 h group (0%). Adverse events included 30 cases in the 0 h group, 42 in the 0–48 h group, and 67 in the >48 h group, with statistically significant differences in hemoglobin reduction, headache/dizziness, and liver injury. No significant differences were found in digestive and skin-related reactions. Conclusions: The results suggest that the >48 h transition regimen may show some advantages in efficacy but also increases the risk of adverse reactions significantly. Therefore, it is recommended to complete the intravenous-to-oral switch carefully with blood drug concentrations strictly monitored. Full article

Soft-sediment deformation structures (SSDSs) typically form in unconsolidated sedimentary deposits before lithification. Understanding these structures involves evaluating their characteristics, genesis timing, and the dynamics of sediment deformation. SSDSs are essential for deciphering ancient environments, reconstructing depositional processes, and discerning past prevailing conditions. In the Dead Sea region, SSDSs are abundant and well preserved due to unique geological and environmental factors, including rapid sedimentation rates and seismic activity. Influenced by the Dead Sea Transform Fault, the area offers insights into tectonic activity and historical earthquakes predating modern instrumentation. This study extensively examines SSDSs along the Dead Sea area in Jordan, focusing on sediments near the Lisan Peninsula, where the prominent Lisan Formation (71–12 ka) exposes numerous deformations. Mineralogical and geochemical analyses using X-ray diffraction (XRD) and X-ray fluorescence (XRF) were applied on deformed and undeformed layers to test the potential trigger of seismite formation in the Dead Sea area. The XRD and XRF results reveal Aragonite and Halite as the predominant compounds. Field observations, coupled with mineralogical and geochemical data, suggest tectonic activity as the primary driver of SSDSs formation in the Dead Sea region. Other contributing factors, such as high salinity, arid climate, and depositional settings, may also have influenced their formation. These structures offer valuable insights into the region’s geological history, environmental conditions, and tectonic evolution. Full article

From the 1970s, the Dead Sea experienced severe halo-karstification and anthropogenic modifications. Progressively, but at an accelerating rate, subsidence, landslides, and sinkholes have increased in number and magnitude. The hazards’ triggering factors are the terminal lake level lowering at more than one meter per year and the dynamic equilibrium of the hydrogeological system. Over the Lisan peninsula, archived satellite images revealed the extent of the damaged areas. On 22 March 2000, the destruction of dike 19 represented a loss of 38 M USD. This is the most important event recorded since the beginning of the Dead Sea recession some 50 years ago. In 2018, a rehabilitation project of that dike started. This research analyses the viability of the reinstatement works. The advanced space borne radar interferometry technique is applied to map ground deformations before and during the project. This article reveals that the ongoing rehabilitation and reinstatement works of dike 19 are threatened by ongoing halo-karstification processes. Field observations and subsidence/uplift dynamics support this statement. The past experiences are taken into consideration to adapt industrial expansion strategies. However, the permeability of the salt pan floor could trigger a fast development of a karst system able to destroy the rehabilitated dike 19. Full article

Global aging is getting worse, especially in China, a country with a large population. It is urgently needed to plan the site of new urban elderly care facilities for an aging society. Based on point of interest data and machine learning algorithms, we established a site selection model of urban elderly care facilities for Wuhan in China and selected potential optimal sites for new urban elderly care facilities. We found that 2059 of the 31,390 grids with a resolution of 500 m × 500 m of Wuhan are priority layout grids for new urban elderly care facilities. A total of 635 priority grids were further selected based on the agglomeration degree of the aging population in each street. They are mainly distributed in the areas with a concentrated aging population within the Second Ring Road around the urban centers. Additionally, some outer suburban streets with a relatively high aging degree also require immediate facility construction. The point of interest data and machine learning algorithms to select the location of urban elderly care facilities can optimize their overall configuration and avoid the subjectivity of site selection to some degree, provide empirical support for how to achieve a good configuration of “population–facilities” in space, and continuously improve the science of the spatial allocation of elderly care facilities. Full article

Lake Rawapening, Semarang Regency, Indonesia, has incorporated a holistic plan in its management practices. However, despite successful target achievements, some limitations remain, and a review of its management plan is needed. This paper identifies and analyzes existing lake management strategies as a standard specifically in Lake Rawapening by exploring various literature, both legal frameworks and scholarly articles indexed in the Scopus database and Google Scholar about lake management in many countries. By using Publish or Perish with the keywords “lake management” OR “management of lake”, 1532 and 1990 works from the Scopus database and Google Scholar, respectively, have been reduced 37. The results show that there are two major types of lake management, namely pillar-based and object-based. The holistic review has resulted in nine points of pillar-based management, which consists of conceptual paradigms as the foundation, and 11 points of object-based management to restore or preserve the lake, which is in line with the form of programs and activities. Overall, Lake Rawapening management should be concerned with finance and technology when applying pillar-based management, and it should include more activities within programs on erosion-sedimentation control as well as monitoring of operational performance using information systems to ensure the implementation of activities within programs in applying object-based lake management. Full article

The development of transoral laser microsurgery (TLM) was an important step in the history of conservative laryngeal surgery. TLM reported comparable oncological outcomes and better functional postoperative and rehabilitation outcomes than open partial laryngectomy. TLM is currently considered as the standard surgical approach for early-stage laryngeal carcinoma. However, TLM has many limitations, including the limited view of the surgical field through the laryngoscope, exposure difficulties for some tumor locations, and a long learning curve. The development of transoral robotic surgery (TORS) appears to be an important issue to overcome these limitations. The current robotic technologies used in surgery benefited from the research of the U.S. Military and National Aeronautics and Space Administration (NASA) in the 1970s and 1980s. The first application in humans started in the 2000s with the first robotic-assisted cholecystectomy in the US, performed by a surgeon located in France. The use of robots in otolaryngology occurred after the development of the Da Vinci system in digestive surgery, urology, and gynecology, and mainly concerns cT1-T2 and some selected cT3 oropharyngeal and supraglottic carcinomas. With the development of a new robotic system with smaller arms and instruments, TORS indications will probably evolve in the next few years, leading to better outcomes for laryngeal or hypopharyngeal carcinomas. Full article

Historically, surgery was the first-choice therapy for early, intermediate and advanced laryngeal squamous cell carcinoma (LSCC). Partial laryngeal surgery has evolved in recent decades and was influenced by many historic events and the development of new technologies. Partial laryngectomies may be performed by open, endoscopic or transoral robotic approaches. In this historic paper, we describe the evolution of open partial laryngectomy techniques, indications and surgical outcomes. Since the first partial laryngectomy in 1788, many U.S., U.K. and European surgeons, including Henry Sands, Jacob da Silva Solis-Cohen and Theodor Billroth, performed this surgical procedure under local anesthesia for tuberculosis, cancer or syphilis. Partial laryngectomy gained reputation in the medical community in 1888 due to the laryngeal cancer and death of the prince of Prussia, Frederick III. Frederick III’s death represented the turning point in the history of partial laryngectomies, calling attention to the importance of semiotics, biopsy and early diagnosis in laryngeal cancers. Hemi-laryngectomy was indicated/proposed for lateral laryngeal tumors, while thyrotomy was indicated for cancers of the middle part of the vocal fold. The second landmark in the history of partial laryngectomies was the discovery of cocaine, novocaine and adrenaline and the related development of local anesthetic techniques, which, together with the epidemiological and hygienic advances of the 19th century, allowed for better perioperative outcomes. General anesthesia was introduced in the second part of the 20th century and further improved the surgical outcomes. The diagnosis of laryngeal cancer was improved with the development of X-rays and direct laryngoscopies. The 20th century was characterized by the development and improvement of vertical partial laryngectomy procedures and the development of horizontal partial laryngectomies for both supraglottic and glottic regions. The history and the evolution of these techniques are discussed in the present historical paper. Full article

The future extraction of mineral resources may irreversibly damage ocean floor geodiversity in the Southwest Pacific Ocean. Therefore, understanding of the spatial distribution of ocean floor geodiversity in relation to mineral resources is important. For that purpose, we first developed a geodiversity index map of the western Pacific Ocean including spatial information of openly available digital layers of four components: seafloor geomorphology, sediment thickness, bathymetry and seafloor roughness. Second, we analysed how these components contributed to the geodiversity index. Finally, correlations between three mineral resources (seafloor massive sulphides, polymetallic nodules and cobalt-rich crusts) and the geodiversity index, its components, and the ocean floor age were calculated. The results showed that the ocean floor environment and the time necessary for the formation of the three mineral resources were predominantly related to the bathymetry component and the age of the ocean floor, and to a lesser extent to the seafloor roughness, geomorphology and sediment thickness components. We conclude that the ocean floor geodiversity index and its components contribute to an improved understanding of the spatial distribution of abiotic seafloor diversity and can be optimized by using higher resolution data. We suggest that ocean floor geodiversity could be considered in future resource extraction to support responsible mining and help limit environmental damage. Full article

This study provides the first full characterization of decadal changes of surface winds over 10 marginal seas along the Eurasian continent using satellite wind observations. During the three decades (1988–2018), surface warming has occurred in all seas at a rate more pronounced in the South European marginal seas (0.4–0.6 °C per decade) than in the monsoon-influenced North Indian and East Asian marginal seas (0.1–0.2 °C per decade). However, surface winds have not strengthened everywhere. On a basin average, winds have increased over the marginal seas in the subtropical/mid-latitudes, with the rate of increase ranging from 11 to 24 cms⁻¹ per decade. These upward trends reflect primarily the accelerated changes in the 1990s and have largely flattened since 2000. Winds have slightly weakened or remained little changed over the marginal seas in the tropical monsoonal region. Winds over the Red Sea and the Persian Gulf underwent an abrupt shift in the late 1990s that resulted in an elevation of local wind speeds. The varying relationships between wind and SST changes suggest that different marginal seas have responded differently to environmental warming and further studies are needed to gain an improved understanding of climate change on a regional scale. Full article

This work presents a simple and innovative protocol employing a microfluidic paper-based analytical device (µPAD) for equipment-free determination of mercury. In this method, mercury (II) forms an ionic-association complex of tetraiodomercurate (II) ion (HgI₄²⁻_(aq)) using a known excess amount of iodide. The residual iodide flows by capillary action into a second region of the paper where it is converted to iodine by pre-deposited iodate to liberate I_2(g) under acidic condition. Iodine vapor diffuses across the spacer region of the µPAD to form a purple colored of tri-iodide starch complex in a detection zone located in a separate layer of the µPAD. The digital image of the complex is analyzed using ImageJ software. The method has a linear calibration range of 50–350 mg L⁻¹ Hg with the detection limit of 20 mg L⁻¹. The method was successfully applied to the determination of mercury in contaminated soil and water samples which the results agreed well with the ICP-MS method. Three soil samples were highly contaminated with mercury above the acceptable WHO limits (0.05 mg kg⁻¹). To the best of our knowledge, this is the first colorimetric µPAD method that is applicable for soil samples including mercury contaminated soils from gold mining areas. Full article

Satellite observations of sea surface salinity (SSS) have been validated in a number of instances using different forms of in situ data, including Argo floats, moorings and gridded in situ products. Since one of the most energetic time scales of variability of SSS is seasonal, it is important to know if satellites and gridded in situ products are observing the seasonal variability correctly. In this study we validate the seasonal SSS from satellite and gridded in situ products using observations from moorings in the global tropical moored buoy array. We utilize six different satellite products, and two different gridded in situ products. For each product we have computed seasonal harmonics, including amplitude, phase and fraction of variance (R²). These quantities are mapped for each product and for the moorings. We also do comparisons of amplitude, phase and R² between moorings and all the satellite and gridded in situ products. Taking the mooring observations as ground truth, we find general good agreement between them and the satellite and gridded in situ products, with near zero bias in phase and amplitude and small root mean square differences. Tables are presented with these quantities for each product quantifying the degree of agreement. Full article

Active commuting to school is highly recommended for several reasons, and in the decision-making process for doing so, a child interacts with parents and teachers. Until now, these three interactors’ gender-specific perspectives on children and adolescents’ need for cycling to school have been unavailable. Thus, our concept mapping study analyzed the needs of 12- to 15-year-olds in Germany for cycling to and from school daily, as perceived by students, parents, and teachers stratified by gender. From November 2019 to February 2020, 136 students, 58 parents, and 29 teachers participated. Although 87.8% of girls and 100% of boys owned a bicycle, only 44.4% of girls and 72.9% of boys cycled to school. On average, girls cycled to school on 1.6 ± 2.0 days a week and boys on 2.7 ± 2.0 days a week. A “bicycle and related equipment,” the “way to school,” and “personal factors” were reported needs, perceived by students and teachers of both genders and by mothers. Girls reported the additional gender-specific need for “social behavior in road traffic,” mothers and female teachers reported “role of parents,” and female teachers reported a “sense of safety.” This study’s findings could inspire the development of school-based bicycle interventions. Full article

Satellite remote sensing of sea surface salinity (SSS) in the recent decade (2010–2019) has proven the capability of L-band (1.4 GHz) measurements to resolve SSS spatiotemporal variability in the tropical and subtropical oceans. However, the fidelity of SSS retrievals in cold waters at mid-high latitudes has yet to be established. Here, four SSS products derived from two satellite missions were evaluated in the subpolar North Atlantic Ocean in reference to two in situ gridded products. Harmonic analysis of annual and semiannual cycles in in situ products revealed that seasonal variations of SSS are dominated by an annual cycle, with a maximum in March and a minimum in September. The annual amplitudes are larger (>0.3 practical salinity scale (pss)) in the western basin where surface waters are colder and fresher, and weaker (~0.06 pss) in the eastern basin where surface waters are warmer and saltier. Satellite SSS products have difficulty producing the right annual cycle, particularly in the Labrador/Irminger seas where the SSS seasonality is dictated by the influx of Arctic low-salinity waters along the boundary currents. The study also found that there are basin-scale, time-varying drifts in the decade-long SMOS data records, which need to be corrected before the datasets can be used for studying climate variability of SSS. Full article

Many children do not meet the recommendations for healthy sleep, which is concerning given the potential negative effects on children’s health. To promote healthy sleep, it is crucial to understand its determinants. This concept mapping study therefore explores perspectives of children and parents on potential determinants of children’s inadequate sleep. The focus lies on 9–12 year old children (n = 45), and their parents (n = 33), from low socioeconomic neighbourhoods, as these children run a higher risk of living in a sleep-disturbing environment (e.g., worries, noise). All participants generated potential reasons (i.e., ideas) for children’s inadequate sleep. Next, participants sorted all ideas by relatedness and rated their importance. Subsequently, multidimensional scaling and hierarchical cluster analyses were performed to create clusters of ideas for children and parents separately. Children and parents both identified psychological (i.e., fear, affective state, stressful situation), social environmental (i.e., sleep schedule, family sleep habits), behavioural (i.e., screen behaviour, physical activity, diet), physical environmental (i.e., sleep environment such as temperature, noise, light), and physiological (i.e., physical well-being) determinants. These insights may be valuable for the development of future healthy sleep interventions. Full article