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The near‐surface boundary layer can mediate the response of mountain glaciers to external climate, cooling the overlying air and promoting a density‐driven glacier wind. The fundamental processes are conceptually well understood, though the magnitudes of cooling and presence of glacier winds are poorly quantified in space and time, increasing the forcing uncertainty for melt models. We utilize a new data set of on‐glacier meteorological measurements on three neighboring glaciers in the Swiss Alps to explore their distinct response to regional climate under the extreme 2022 summer. We find that synoptic wind origins and local terrain modifications, not only glacier size, play an important role in the ability of a glacier to cool the near‐surface air. Warm air intrusions from valley or synoptically‐driven winds onto the glacier can occur between ∼19% and 64% of the time and contribute between 3% and 81% of the total sensible heat flux to the surface during warm afternoon hours, depending on the fetch of the glacier flowline and its susceptibility to boundary layer erosion. In the context of extreme summer warmth, indicative of future conditions, the boundary layer cooling (up to 6.5°C cooler than its surroundings) and resultant katabatic wind flow are highly heterogeneous between the study glaciers, highlighting the complex and likely non‐linear response of glaciers to an uncertain future. The presence of a 0°C ice surface cools the near‐surface air and generates a unique micro‐climate that complicates a glaciers response to future warming. Using a new data series on three glaciers during an extreme summer of 2022, we explore how variable this cooling is in space and time and investigate the factors that can control it. We focus largely on the role of valley and synoptic winds that are found to affect glaciers of varying size and orientation differently, influencing the amount of heat transfer to the ice surface that glaciers receive from outside its own micro‐climate. Moreover, we find that the presence of glacier winds can act to enhance or reduce overall heat transfer to the glacier, depending on the wind strength and degree of boundary layer disruption. We highlight the complexities that are ignored in simpler melt modeling frameworks and demonstrate how, especially under extreme summer heat, indicative of future conditions, static parameters to relate glacier melt to temperature are likely to be inappropriate. Glacier size and alignment with valley/synoptic wind gradients control the magnitude of near‐surface coolingValley/synoptic winds can occur between 19% and 64% of the time and contribute between 3% and 81% of total sensible heat to the ice surfaceLocalized cooling and turbulence in the boundary layer increase the complexity and non‐linearity of glacier response to climate Glacier size and alignment with valley/synoptic wind gradients control the magnitude of near‐surface cooling Valley/synoptic winds can occur between 19% and 64% of the time and contribute between 3% and 81% of total sensible heat to the ice surface Localized cooling and turbulence in the boundary layer increase the complexity and non‐linearity of glacier response to climate

•Subcutaneous emicizumab administered from birth has the potential to reduce the risk of ICH and joint bleeds before damage occurs.•Primary analysis of the HAVEN 7 trial indicates emicizumab is efficacious and well tolerated in infants with severe HA.

Background:Due to challenges of factor (F)VIII administration, many infants with severe hemophilia A (HA) do not receive prophylaxis until ≥1 year of age. Emicizumab can be administered subcutaneously from HA diagnosis, which may reduce risk of spontaneous and traumatic bleeds, including intracranial hemorrhage. This primary analysis of HAVEN 7 (NCT04431726) evaluates the efficacy, safety, and pharmacokinetics (PK) of emicizumab in infants ≤12 months of age with severe HA without FVIII inhibitors.

Background:Emicizumab, a bispecific antibody that mimics the cofactor function of activated factor (F)VIII, demonstrated a favorable safety and efficacy profile in infants with severe hemophilia A (HA) without FVIII inhibitors in HAVEN 7 (NCT04431726; Pipe et al. Blood 2022, 140[S1]: 457-459). It is known that some coagulation factors including FIX and FX, the binding targets of emicizumab, have lower plasma levels during the first 6 months of life. This research investigates whether the developing coagulation system impacts the pharmacodynamics (PD) of emicizumab prophylaxis in infants with HA enrolled to HAVEN 7 from birth to ≤ 12 months of age.

Introduction

Trust motivates people's uptake and use of digital financial services (DFS). Understanding the socio‐cultural determinants of DFS trust are needed to scale financial access and drive financial inclusion. These are core components of international development strategies, such as the Sustainable Development Goals (SDGs) or Universal Financial Access (UFA2020). The IFC‐Mastercard Foundation Partnership for Financial Inclusion (the Partnership) conducted ethnographic research to understand factors that impact people's attitudes and perceptions of DFS. Nine months of field work each in Cameroon, DRC, Senegal and Zambia were conducted, in collaboration with local research institutes’ Anthropology departments and the African Studies Center at the University of Leiden. The results of the ethnographic research produced a framework for understanding drivers and barriers to people growing trust in digital financial services. This paper analyzes the quantitative and qualitative application of the framework for understanding digital financial services perceptions and uptake propensities for a specific market segment: micro, small to medium‐sized enterprises (MSMEs). The framework guided the design of focus groups and survey instruments, whose data provide a classification of issues business owners face for adopting DFS and the degree to which the socio‐cultural determinants of these issues may drive or hinder DFS adoption. Further, the survey data provide ground‐truth observations that are applied to transactional big data sets toward the development of a model to identify business from individual customers. Identifying MSMEs enables providers to deliver business‐specific DFS services at scale and further enable financial inclusion. It was found that MSMEs could be successfully identified using the big data analytics model, and that the classification of small‐medium (and micro) segments could be further identified by application of the survey data. Using the framework throughout all stages of the analysis further demonstrates the business value that can be obtained by employing the ethnographic approach. Doing so ensured that salient DFS issues relevant to business owners were inherent in survey questions ex‐ante, thereby yielding meaningful results that can be used to engage MSMEs, design relevant products and advance financial inclusion.

High Mountain Asia (HMA) is among the most vulnerable water towers globally and yet future projections of water availability in and from its high‐mountain catchments remain uncertain, as their hydrologic response to ongoing environmental changes is complex. Mechanistic modeling approaches incorporating cryospheric, hydrological, and vegetation processes in high spatial, temporal, and physical detail have never been applied for high‐elevation catchments of HMA. We use a land surface model at high spatial and temporal resolution (100 m and hourly) to simulate the coupled dynamics of energy, water, and vegetation for the 350 km2Langtang catchment (Nepal). We compare our model outputs for one hydrological year against a large set of observations to gain insight into the partitioning of the water balance at the subseasonal scale and across elevation bands. During the simulated hydrological year, we find that evapotranspiration is a key component of the total water balance, as it causes about the equivalent of 20% of all the available precipitation or 154% of the water production from glacier melt in the basin to return directly to the atmosphere. The depletion of the cryospheric water budget is dominated by snow melt, but at high elevations is primarily dictated by snow and ice sublimation. Snow sublimation is the dominant vapor flux (49%) at the catchment scale, accounting for the equivalent of 11% of snowfall, 17% of snowmelt, and 75% of ice melt, respectively. We conclude that simulations should consider sublimation and other evaporative fluxes explicitly, as otherwise water balance estimates can be ill‐quantified. The Himalayan mountains are a crucial source of water for local communities and the densely populated lowlands. Snow and glaciers are important for the water cycle in mountains, and many studies have focused on them. However, vegetation can play a central role, too. To better understand the water cycle in a high‐elevation Himalayan basin, we use a computer model that considers physical processes of snow and glaciers, soil, and vegetation in high detail. We simulate the catchment water balance and investigate the importance of single components at different elevations and in different seasons. We find that the transfer of water, in vapor form from the ground, snow and ice and the transpiration of plants are important for the water budget in the study basin, causing more water to return to the atmosphere than ice melt contributing to river runoff. Above 6,500 m above sea level, it is the transformation of snow into water vapor and below 4,000 m the transpiration from vegetation that dominate the water budget. We conclude that models simulating the water cycle in high mountain regions should consider vapor fluxes, as otherwise estimates of the water balance can be misleading. Land surface modeling reveals high altitudinal/subseasonal variability in water balance partitioning in a glacierized Himalayan catchmentWater loss through evapotranspiration, dominated by snow sublimation, exceeds water production from glacier melt by 59% at catchment scaleDepletion of cryospheric water budget is dominated by snow melt, but at high elevations is primarily dictated by snow and ice sublimation Land surface modeling reveals high altitudinal/subseasonal variability in water balance partitioning in a glacierized Himalayan catchment Water loss through evapotranspiration, dominated by snow sublimation, exceeds water production from glacier melt by 59% at catchment scale Depletion of cryospheric water budget is dominated by snow melt, but at high elevations is primarily dictated by snow and ice sublimation

The presence of a developed boundary layer decouples a glacier's response from ambient conditions, suggesting that sensitivity to climate change is increased by glacier retreat. To test this hypothesis, we explore six years of distributed meteorological data on a small Swiss glacier in the period 2001–2022. Large glacier fragmentation has occurred since 2001 (−35% area change up to 2022) coinciding with notable frontal retreat, an observed switch from down‐glacier katabatic to up‐glacier valley winds and an increased sensitivity (ratio) of on‐glacier to off‐glacier temperature. As the glacier ceases to develop density‐driven katabatic winds, sensible heat fluxes on the glacier are increasingly determined by the conditions occurring outside the boundary layer of the glacier, sealing the glacier's demise as the climate continues to warm and experience an increased frequency of extreme summers. Down‐glacier winds promote a unique micro‐climate, maintaining relatively lower temperatures over the surface of mountain glaciers. Using six years of meteorological data in the period 2001–2022, we observe increases in the relative changes of above‐ice air temperatures compared to temperatures outside the glacier. As the glacier ceases to develop its own micro‐climate, warmer winds generated by heated valley slopes increasingly control the amount of heat transfer to melt glacier ice. This work offers new observational evidence that suggests that, as glaciers continue to shrink and fragment, they becoming increasingly sensitive to future climate warming. On‐glacier air temperatures have become more sensitive to ambient temperatures in a warming climateUp‐valley winds have increased >20% between 2001 and 2021, making sensible heat fluxes more dependent on conditions outside the glacierThe decay of the katabatic system due to glacier retreat indicates a nonlinear sensitivity of the glacier to continued warming On‐glacier air temperatures have become more sensitive to ambient temperatures in a warming climate Up‐valley winds have increased >20% between 2001 and 2021, making sensible heat fluxes more dependent on conditions outside the glacier The decay of the katabatic system due to glacier retreat indicates a nonlinear sensitivity of the glacier to continued warming

Ice cliff distribution plays a major role in determining the melt of debris‐covered glaciers but its controls are largely unknown. We assembled a data set of 37,537 ice cliffs and determined their characteristics across 86 debris‐covered glaciers within High Mountain Asia (HMA). We find that 38.9% of the cliffs are stream‐influenced, 19.5% pond‐influenced and 19.7% are crevasse‐originated. Surface velocity is the main predictor of cliff distribution at both local and glacier scale, indicating its dependence on the dynamic state and hence evolution stage of debris‐covered glacier tongues. Supraglacial ponds contribute to maintaining cliffs in areas of thicker debris, but this is only possible if water accumulates at the surface. Overall, total cliff density decreases exponentially with debris thickness as soon as the debris layer reaches a thickness of over 10 cm. Debris‐covered glaciers are common throughout the world's mountain ranges and are characterized by the presence of steep ice cliffs among the debris‐covered ice. It is well‐known that the cliffs are responsible for a large portion of the melt of these glaciers but the controls on their formation, development and distribution across glaciers remains poorly understood. Novel mapping approaches combined with high‐resolution satellite and drone products enabled us to disentangle some of these controls and to show that the ice cliffs are generally formed and maintained by the surface hydrology (ponds or streams) or by the opening of crevasses. As a result, they depend both at the local and glacier scale on the dynamic state of the glaciers as well as the evolution stage of their debris cover. This provides a pathway to better represent their contribution to glacier melt in predictive glacier models. We derived an unprecedented data set of 37,537 ice cliffs and their characteristics across 86 debris‐covered glaciers in High Mountain AsiaWe find that 38.9% of the cliffs are stream‐influenced, 19.5% pond‐influenced and 19.7% are crevasse‐originatedIce cliff distribution can be predicted by velocity, as an indicator of the dynamics and state of evolution of debris‐covered glaciers We derived an unprecedented data set of 37,537 ice cliffs and their characteristics across 86 debris‐covered glaciers in High Mountain Asia We find that 38.9% of the cliffs are stream‐influenced, 19.5% pond‐influenced and 19.7% are crevasse‐originated Ice cliff distribution can be predicted by velocity, as an indicator of the dynamics and state of evolution of debris‐covered glaciers

We use high‐resolution digital elevation models (DEMs) from unmanned aerial vehicle (UAV) surveys to document the evolution of four ice cliffs on the debris‐covered tongue of Lirung Glacier, Nepal, over one ablation season. Observations show that out of four cliffs, three different patterns of evolution emerge: (i) reclining cliffs that flatten during the ablation season; (ii) stable cliffs that maintain a self‐similar geometry; and (iii) growing cliffs, expanding laterally. We use the insights from this unique data set to develop a 3‐D model of cliff backwasting and evolution that is validated against observations and an independent data set of volume losses. The model includes ablation at the cliff surface driven by energy exchange with the atmosphere, reburial of cliff cells by surrounding debris, and the effect of adjacent ponds. The cliff geometry is updated monthly to account for the modifications induced by each of those processes. Model results indicate that a major factor affecting the survival of steep cliffs is the coupling with ponded water at its base, which prevents progressive flattening and possible disappearance of a cliff. The radial growth observed at one cliff is explained by higher receipts of longwave and shortwave radiation, calculated taking into account atmospheric fluxes, shading, and the emission of longwave radiation from debris surfaces. The model is a clear step forward compared to existing static approaches that calculate atmospheric melt over an invariant cliff geometry and can be used for long‐term simulations of cliff evolution and to test existing hypotheses about cliffs' survival. We use high‐resolution digital elevation models to document the evolution of supraglacial ice cliffs over one ablation seasonReclining cliffs that flatten, stable cliffs maintaining a self‐similar geometry, and growing cliffs that expand laterally are observedWe develop a 3‐D model of cliff backwasting driven by atmospheric melt, reburial by surrounding debris, and the effect of adjacent ponds

In the late 1990s, the entire population of the Aksay Kazakh Autonomous County in Gansu, China, was resettled to the newly built town of Hongliuwan. About one-third of Aksay’s Kazakh population had already left before the resettlement started, migrating predominantly to Kazakhstan. In order to keep the favourable status of an Autonomous County, the remaining Kazakhs had to be persuaded to stay. This paper argues that by building the new town, the Chinese state has considerably shaped its citizen’s decision-making process regarding migration. The state has offered appealing options regarding financial safety and a modern lifestyle, so that most Kazakhs in Hongliuwan would see no reason to leave anymore. This case presents an example of how the Chinese state impacts the decisions of its citizens by manifesting itself in an urban context.

There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO•), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO•, one produced by endothelial cells stimulated with carbachol in vitro and another using the NO•‐donor S‐nitroso‐N‐acetyl‐d,l‐penicillamine (SNAP) in vivo. Two main NO•effects were observed: proliferation of HSCs—especially of the short‐term HSCs—and its commitment and terminal differentiation to the myeloid lineage. NO•‐induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki‐67, upregulation of Notch‐1, Cx43, PECAM‐1, CaR, ERK1/2, Akt, p38, PKC, and c‐Myc. NO•‐induced HSCs differentiation was characterized by the increase in granulocytic‐macrophage progenitors, granulocyte–macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA‐3and Ikz‐3genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO•in inducing HSCs proliferation and myeloid differentiation involving multiple signaling. StemCells2014;32:2949–2960

Die Behandlung der Adipositas ist aufgrund der multifaktoriellen Genese komplex. Das Therapiekonzept muss deshalb auf die individuellen Bedürfnisse und Problembereiche des Betroffenen zugeschnitten sein und ist von verschiedenen Faktoren wie Ausmaß des Übergewichts, dem Vorliegen körperlicher Folgeerkrankungen und psychischer Komorbidität, den bisher erfolgten Behandlungsmaßnahmen sowie von Motivationsfaktoren der Patientinnen und Patienten abhängig. Vor der Entscheidung zu einer Therapiemaßnahme ist eine strukturierte Diagnostik in Kooperation verschiedener Fachdisziplinen (Psychosomatik/Psychiatrie/Psychotherapie, Endokrinologie, Sportmedizin, Ernährungsmedizin und Chirurgie) unverzichtbar. Die Therapie muss multidisziplinär erfolgen und beinhaltet neben einer adäquaten Therapie der Komorbiditäten zuweilen auch eine psychopharmakologische Unterstützung. Die Erfolge der konservativen Therapie der Adipositas sind bemerkenswert und langdauernd und können sich aus finanzieller wie auch aus ethischen Überlegungen durchaus mit denjenigen der Adipositaschirurgie sehen lassen, wenngleich letztere für Patienten (und Ärzte) oft den Anreiz des raschen Erfolges trägt.

In recent years, the antitumoral activity of antimicrobial peptides (AMPs) has been the goal of many research studies. Among AMPs, gomesin (Gm) displays antitumor activity by unknown mechanisms. Herein, we studied the cytotoxicity of Gm in the Chinese hamster ovary (CHO) cell line. Furthermore, we investigated the temporal ordering of organelle changes and the dynamics of Ca2+signaling during Gm-induced cell death. The results indicated that Gm binds to the plasma membrane and rapidly translocates into the cytoplasm. Moreover, 20 μM Gm increases the cytosolic Ca2+and induces membrane permeabilization after 30 min of treatment. Direct Ca2+measurements in CHO cells transfected with the genetically encoded D1-cameleon to the endoplasmic reticulum (ER) revealed that Gm induces ER Ca2+depletion, which in turn resulted in oscillatory mitochondrial Ca2+signal, as measured in cells expressing the genetically encoded probe to the mitochondrial matrix mitPericam. This leads to mitochondria disruption, loss of mitochondrial membrane potential and increased reactive oxygen species prior to membrane permeabilization. Gm-induced membrane permeabilization by a Ca2+-dependent pathway involving Gm translocation into the cell, ER Ca2+depletion and disruption, mitochondrial Ca2+overload and oxidative stress.

Die Schweiz weist im Europäischen Quervergleich mit 23.5 % (2009) den höchsten Anteil an Ausländern auf. Der europäische Durchschnittsanteil beträgt andererseits lediglich zwischen 7.3 bis 8.6 %. Deshalb ist es für den praktisch tätigen Arzt wichtig, die Besonderheiten ausländischer Patientengruppen zu kennen. Der Einfluss der Persönlichkeit (Erleben, Verhalten) ist nicht unabhängig vom Einfluss kulturell bedingter Umweltfaktoren (regional unterschiedliche Ernährung, Schadstoffe, Bedeutungen u.a). Zudem beurteilen unterschiedliche kulturelle Gruppen auch die Lebensqualität unterschiedlich. Als psychologische Ursachen rezidivierender abdominaler Schmerzen stehen Belastungen (life events), Effekte der Automedikation (Laxantien, Kokain) und sexueller Missbrauch im Vordergrund; allerdings sind auch (seltene) infektiöse Ursachen bei Immigranten häufiger (z. B. Tbc, Histoplasmose etc.). Migrationsspezifische Besonderheiten sind vor allem in der Semiotik der Beschwerden zu suchen: nicht jeder Abdominalschmerz ist Schmerz im Abdomen gleichzusetzen. Schließlich ist es zentral, die Unterscheidung zwischen organischen, funktionellen und psychologisch-bedingten Schmerzen vorzunehmen. Diese lässt sich aber zumeist nur im Kontext der Gesamtsituation eines Patienten zuverlässig eruieren und erfordert je nach Situation die Unterstützung eines Kollegen aus dem entsprechenden Kulturkreis oder eines erfahrenen Dolmetschers. In dieser Übersicht beschränken wir uns auf die Darstellung der arbeitenden Migrationsbevölkerung, weil sie den größten Anteil aller Migranten ausmacht. Die Besonderheiten von Asylsuchenden werden jedoch, wo sinnvoll, ebenfalls beleuchtet.

The article focuses on tapestries that show the life of Alexander the Great exhibited at the 2008 Antiques and Fine Arts Fair of Belgium in Brussels and at a permanent exhibition in the Palazzo del Principe in Genoa. The "Story of Alexander the Great" tapestries were woven with fine woollen yarns as well as silk, gold and silver threads. These feature the scenes from Alexander's youth including Alexander beneath the gaze of God the Father, Alexander taming the horse and Alexander's army overcoming a wildman at the edge of the world.