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Study abroad is often hailed as a unique and important learning experience that fosters students' ability to engage in effective and appropriate interactions in a variety of cultural contexts. Scholars, however, have not only questioned the learning that occurs in study abroad but have also highlighted problematic aspects such as the potential miseducation of participants and harm to host communities, particularly for short-term study abroad (STSA) experiences. Utilizing the lens of criticalhope, the purpose of this study was to critically assess the potential of STSA in fostering cross-cultural learning, while also examining its limitations and potential harm. Based on interviews with 18 participants 1 and 2 years after their STSA, we found STSA has the potential to be a catalyst for learning and growth related to the attitudes, knowledge, and skills needed for effective cross-cultural interactions. However, when participants approached STSA with a colonial attitude and failed to connect learning to cross-cultural experiences after STSA, that learning was minimal and STSA reinforced ethnocentric viewpoints. Participants' race and ethnicity shaped their learning. Black, Indigenous, and People of Color participants who had positive experiences abroad felt inspired by STSA to seek out additional cross-cultural interactions, which led to further growth. The white participants who experienced more growth had passions and interests related to cultural learning prior to STSA and engaged in meaningful cross-cultural experiences after STSA. In our Implications section, we discuss ways to maximize the potential of STSA to foster cross-cultural learning and serve as a catalyst for social change.

BACKGROUND: Frontal craniotomies for a medial subfrontal approach necessitate crossing the frontal sinus. Large superior extensions of the frontal sinus into frontal bone can result in mucosal retention in a free craniotomy bone flap, leading to a delayed mucocele with significant associated morbidity. The authors describe an open-window craniectomy technique that permits mucosal removal under direct vision and maintains the inner table on the bone flaps inferior side, helping to seal off the sinus opening with a pericranial flap. OBSERVATIONS: An illustrative case involving a medial right frontal craniotomy for a third ventricle mass in a patient with a large superior extension of the frontal sinus into frontal bone is presented. After creating a free frontal bone flap, the inner table was drilled out to the margins of the frontal sinus cavity and any remaining mucosa was cleared. A portion of the inner table above the bone flaps inferior margin was left in place, resembling an open window when viewed from the inner table side. The remaining anterior and posterior wall of the flap inferiorly provided a matched surface for the opening into the remaining frontal sinus, which was covered by pericranium. Long-term follow-up indicated no major complications or delayed mucocele. LESSONS: The open-window craniectomy technique can be considered for frontal sinus violations in patients with large superior frontal bone extension.

Abstract Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have tumor-targeting potential. We modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by ATAC-seq and RNA-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations. HNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound-healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue. Cornification was frequently found surrounding necrotic areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators activated the differentiation program in primary HNSCC cells. In HNSCC tissue, distinct cell differentiation states were found to create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon faithful HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection.

The impact of a slightly modified broadband snow surface albedo parameterization, which explicitly considers the cloud dependence of the snow albedo, is evaluated in simulations of a coupled regional climate model of the Arctic. The cloud dependence of the snow albedo leads to a more realistic simulation of the variability of the surface albedo during the snowmelt period in late May and June. In particular, the reproduction of lower albedo values under cloud-free/broken-cloud conditions during the snowmelt period represents an improvement and results in an earlier disappearance of the snow cover and an earlier onset of sea-ice melt. In this way, the consideration of the cloud dependence of the snow albedo results in an amplification of the two-stage snow/ice albedo feedback in the model. This finds expression in considerably increased sea-ice melt during the summer months and ends up in a new quasi-stationary equilibrium in sea ice with statistically significant lower sea-ice volume and statistically significant lower summer sea-ice area.

Abstract Background High levels of maternal morbidity and mortality persist in low- and middle-income countries, despite increases in coverage of facility delivery and skilled assistance at delivery. We compared levels of facility birth to a summary delivery care measure and quantified gaps. Methods We approximated a delivery care score from type of delivery (home, lower-level facility, or hospital), skilled attendant at delivery, a stay of 24-or-more-hours after delivery, and a health check within 48-h after delivery. Data were obtained from 333,316 women aged 15–49 who had a live birth in the previous 2 years, and from 71 countries with nationally representative surveys between 2013 and 2020. We computed facility delivery and delivery care coverage estimates to assess the gap. We stratified the analysis by country characteristics, including the national maternal mortality ratio (MMR), to assess the size of coverage gaps, and we assessed missed opportunities through coverage cascades. We looked at the association between MMR and delivery care coverage. Results Delivery care coverage varied by country, ranging from 24% in Sudan to 100% in Cuba. Median coverage was 70% with an interquartile range of 30 percentage points (55% and 85%). The cascade showed that while 76% of women delivered in a facility, only 41% received all four interventions. Coverage gaps exist across all MMR levels. Gaps between highest and lowest wealth quintiles were greatest in countries with MMR levels of 100 or higher, and the gap narrowed in countries with MMR levels below 100. The delivery care indicator had a negative association with MMR. Conclusions In addition to providing high-quality evidenced-based care to women during birth and the postpartum period, there is also a need to address gaps in delivery care, which occur within and between countries, wealth quintiles, and MMR phases.

Hydrangea serrata, also knowen as the Japanese tea hortensia, is known for its sweet taste and health properties of bevarages produced from this plant. The H. serrata 3,4-dihydroisocoumarins, hydrangenol and phyllodulcin harbour a variety of biological activities and pharmacological properties. Therefore, a detailed understanding of dihydroisocoumarin biosynthesis in H. serrata is of major interest. Their biosynthesis is assumed to be enhanced by elicitors and mediated by polyketide synthases like in cases of phenylpropanoid derived phytoalexins. A de-novo transcriptome assembly of leaves and roots from the aluminium chloride treatment group versus the control group alongside with annotation was generated. Secondary plant metabolites were analysed by LC-MS. It revealed that a terpene synthase and a triterpenoid synthase gene as well as lignin biosynthesis encoding genes were upregulated in roots. Many genes for transporters, glycosyl, and other transferases as well as glycosylases were found to be differentially expressed in both organs. As no differentially expressed polyketide synthase gene homolog was found, the relative leaf and root 3,4-dihydroisocoumarin content was analysed by LC-MS measurement. Although Hydrangea species are known for their aluminium detoxification using phenylpropanoid-derived compounds, the levels of 3,4- dihydroisocoumarins were not enhanced. In this metabolite analysis, an organ- specific accumulation profile of hydrangenol, phyllodulcin, hydrangeic acid and their mono- and di-glycosides was figured out.

Here, we report an individual, eventually diagnosed with HMG-CoA synthase deficiency, who presented with a cyclic vomiting phenotype. HMG-CoA synthase deficiency is a rare disorder affecting ketone body synthesis in which affected individuals typically present at a young age with hypoketotic hypoglycemia, lethargy, encephalopathy, and hepatomegaly, usually triggered by catabolism (e.g., infection or prolonged fasting). This individual presented with recurrent episodes of vomiting and lethargy, often associated with hypoglycemia or hyperglycemia, at 3 years of age. Metabolic labs revealed nonspecific abnormalities in her urine organic acids (showing mild elevation of dicarboxylic acids with relatively low excretion of ketones) and a normal acylcarnitine profile. Given her clinical presentation, as well as a normal upper gastrointestinal series, esophagogastroduodenoscopy with biopsies, and abdominal ultrasound, she was diagnosed with cyclic vomiting syndrome at 3 years of age. Molecular testing completed at 7 years of age revealed a previously reported pathogenic sequence variant (c.1016+1G>A) and a novel likely pathogenic deletion (1.57 kB deletion, including exon 1) within HMGCS2 consistent with HMG-CoA synthase deficiency. This individual’s presentation, mimicking cyclic vomiting syndrome, widens the clinical spectrum of HMG-CoA synthase deficiency. In addition, this case highlights the importance of molecular genetic testing in such presentations, as this rare disorder lacks specific metabolic markers.

Patients with space-occupying lesions adjacent to the superior sagittal sinus (SSS) present several technical considerations. For craniotomies crossing the SSS, a two-part method allows for dissection of the epidural space and dura under direct vision after removing a more lateral parasagittal bone flap. However, when the inner table surface of the medial component of the two-part bone flap is irregular, this can be difficult. We describe a method for channel drilling of the diploic bone, which allows for the piecemeal removal of the inner table using an upbiting rongeur. This article presents the case of meningioma with documented growth and provides a technical note of this technique to facilitate safe dissection of the midline dura. A patient presented with headaches and an anterior one-third parasagittal meningioma with documented growth. She selected surgical removal for treatment. A right frontal two-part parasagittal craniotomy was recommended. The preoperative imaging showed that the frontal bone was thick, with irregularity of the inner table. Intraoperatively, a channel was drilled in the diploic space of the bone, leaving the outer table intact. This provided a thin lip of the inner table that could be dissected over a short distance and then removed with a 2-mm upbiting rongeur. This allowed for further dissection of the dura crossing the midline under direct vision and safe secondary bone piece removal. The dura was opened to the edge of the SSS, allowing full exposure of the parasagittal region and interhemispheric fissure, thus limiting retraction of the medial right frontal lobe. The bone flap was removed in two pieces without a dural tear over the midline in spite of inner table irregularities. A Simpson grade 1 removal was accomplished, including excision of the affected falx, and the postoperative course was uncomplicated. In conclusion, diploic bone channel drilling is a technique that can be used to create a thin lip of the inner table, which can be removed piecemeal for safe dissection of the midline dura crossing the midline.

An accurate representation of the annual evolution of surface albedo of the Arctic Ocean, especially during the melting period, is crucial to obtain reliable climate model predictions in the Arctic. Therefore, the output of the surface albedo scheme of a coupled regional climate model (HIRHAM–NAOSIM) was evaluated against airborne and ground-based measurements. The observations were conducted during five aircraft campaigns in the European Arctic at different times of the year between 2017 and 2022; one of them was part of the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in 2020. We applied two approaches for the evaluation: (a) relying on measured input parameters of surface type fraction and surface skin temperature (offline) and (b) using HIRHAM–NAOSIM simulations independently of observational data (online). From the offline method we found a seasonally dependent bias between measured and modeled surface albedo. In spring, the cloud effect on surface broadband albedo was overestimated by the surface albedo parametrization (mean albedo bias of 0.06), while the surface albedo scheme for cloudless cases reproduced the measured surface albedo distributions for all seasons. The online evaluation revealed an overestimation of the modeled surface albedo resulting from an overestimation of the modeled cloud cover. Furthermore, it was shown that the surface type parametrization contributes significantly to the bias in albedo, especially in summer (after the drainage of melt ponds) and autumn (onset of refreezing). The lack of an adequate model representation of the surface scattering layer, which usually forms on bare ice in summer, contributed to the underestimation of surface albedo during that period. The difference between modeled and measured net irradiances for selected flights during the five airborne campaigns was derived to estimate the impact of the model bias for the solar radiative energy budget at the surface. We revealed a negative bias between modeled and measured net irradiances (median: −6.4 W m−2) for optically thin clouds, while the median value of only 0.1 W m−2 was determined for optically thicker clouds.

The presence of melt ponds on Arctic summer sea ice significantly alters its albedo and thereby the surface energy budget and mass balance. Large-scale observations of melt pond coverage and sea ice albedo are crucial to investigate the role of sea ice for Arctic amplification and its representation in global climate models. We present the new Melt Pond Detection 2 (MPD2) algorithm, which retrieves melt pond, sea ice, and open-ocean fractions as well as surface albedo from Sentinel-3 visible and near-infrared reflectances. In contrast to most other algorithms, our method uses neither fixed values for the spectral albedo of the surface constituents nor an artificial neural network. Instead, it aims for a fully physical representation of the reflective properties of the surface constituents based on their optical characteristics. The state vector X, containing the optical properties of melt ponds and sea ice along with the area fractions of melt ponds and open ocean, is optimized in an iterative procedure to match the measured reflectances and describe the surface state. A major problem in unmixing a compound pixel is that a mixture of half open water and half bright ice cannot be distinguished from a homogeneous pixel of darker ice. In order to overcome this, we suggest constraining the retrieval with a priori information. Initial values and constraint of the surface fractions are derived with an empirical retrieval which uses the same spectral reflectances as implemented in the physical retrieval. The snow grain size and optical thickness change with time, and thus the ice surface albedo changes throughout the season. Therefore, field observations of spectral albedo are used to develop a parameterization of the sea ice optical properties as a function of the temperature history of the sea ice. With these a priori data, the iterative optimization is initialized and constrained, resulting in a retrieval uncertainty of below 8 % for melt pond and 9 % for open-ocean fractions compared to the reference dataset. As reference data for evaluation, a 10 m resolution product of melt pond and open-ocean fraction from Sentinel-2 optical imagery is used.

Without prompt diagnosis and treatment, patients with Lyme disease may develop life threatening multi-organ system complications. As such, we discuss the key diagnostic features of the condition along with patient-specific suggested treatment protocols. Additionally, Lyme disease is reportedly expanding to regions that were previously not impacted, key epidemiological features are outlined. We discuss a patient with severe Lyme disease who presented with widespread cutaneous involvement and atypical pathologic findings within an uncharacteristic geographic region. Erythematous, annular patches and plaques with dusky-to-clear centers were initially observed on the right thigh and later extended to the trunk and bilateral lower extremities. The diagnosis of Lyme disease was made clinically and confirmed with western blot testing that was positive for IgM antibodies. The patient additionally had a history of rheumatoid arthritis, for which he discontinued treatment prior to the current presentation with Lyme disease. During follow up visits, the patient noted lower extremity joint pain. Due to the overlapping clinical features of post-Lyme arthritis and rheumatoid arthritis, key differences are outlined to prevent misdiagnosis. Data revealing trends in the geographic distribution of the disease and possible need for increased surveillance and prevention strategies within previously unaffected areas are discussed.

Virtual exchanges (VEs) are course-based experiences designed to promote global learning, often by integrating cross-cultural interactions and collaborations with people from other areas of the world into coursework in a virtual format. Due to the widespread disruption of the COVID-19 pandemic, VEs have seen an increase in popularity. However, research findings on the effectiveness of VEs are mixed, and limited guidance is available to VE instructors on how to structure and facilitate these programs. The purpose of this paper is to highlight how theories and literature in two distinct areas of scholarship, Intergroup Contact theory and the Community of Inquiry model in online learning, could be applied to VEs to maximize student learning. We discuss each of these theories first and then highlight how they could be applied to VEs using illustrative examples from a pilot study of five VE courses offered at one institution during the summer of 2021.

Background and Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Results: Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. Conclusions: In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Impact and implications: Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.

Background & Aims: Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and may eventually lead to acute-on-chronic liver failure. One important cause of systemic hyperinflammation is a dysregulated overshooting immune response in ascites in the abdominal cavity. In this study, we analyzed the role of CD8+ T cells in the ascites immune compartment. Methods: Peripheral blood and ascites fluid were collected from 50 patients with decompensated cirrhosis. Phenotype and functional responses of CD8+ T cells were analyzed, and obtained data were compared with each other as well as with healthy controls and patients with compensated cirrhosis. Results: High-dimensional flow cytometry revealed that CD8+ T cells are abundant in the ascites of patients with cirrhosis and exhibit a chronically activated bystander phenotype with innate-like functions. Indeed, we identified distinct CXCR6+CD69+ clusters of late effector memory CD8+ T cells that were rarely found in blood and correlated with clinical parameters of disease severity. Moreover, this CD8+ T-cell population was hyperresponsive to innate cytokines and exhibited cytokine-mediated bystander activation. Interestingly, the Janus kinase (JAK) inhibitor tofacitinib was able to effectively block bystander-activated CXCR6+CD69+ CD8+ T cells and significantly suppress effector molecule production. Conclusions: The results indicate that CXCR6+CD69+ CD8+ T cells in ascites are associated with disease severity and may contribute to inflammation in patients with decompensated cirrhosis, suggesting that targeted inhibition of this immune cell subset may be a viable therapeutic option. Impact and Implications: Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and eventually leads to acute-on-chronic liver failure. One important cause of systemic hyperinflammation is a dysregulated overshooting immune response in ascites in the abdominal cavity. In this study, we demonstrate that CXCR6+CD69+ CD8+ T cells are abundant in the ascites of patients with cirrhosis, exhibit a chronically activated bystander phenotype, and correlate with clinical parameters of disease severity. Moreover, we show that the Janus kinase (JAK) inhibitor tofacitinib can effectively block these bystander-activated CXCR6+CD69+ CD8+ T cells, suggesting that targeted inhibition of this immune cell subset may be a potential therapeutic strategy. Clinical trial number: Prospective registry: INFEKTA (DRKS00010664).

In her response to the post by Bernhard Wegener, who criticizes climate lawsuits as ineffective globules, Manuela Niehaus illustrates the effect of climate lawsuits. She argues that not everything that tastes sweet is just ineffective homeopathy.

Abstract A prevalent side-reaction of succinate dehydrogenase oxidizes malate to enol-oxaloacetate (OAA), a metabolically inactive form of OAA that is a strong inhibitor of succinate dehydrogenase. We purified from cow heart mitochondria an enzyme (OAT1) with OAA tautomerase (OAT) activity that converts enol-OAA to the physiological keto-OAA form, and determined that it belongs to the highly conserved and previously uncharacterized Fumarylacetoacetate_hydrolase_domain-containing protein family. From all three domains of life, heterologously expressed proteins were shown to have strong OAT activity, and ablating the OAT1 homolog caused significant growth defects. In Escherichia coli, expression of succinate dehydrogenase was necessary for OAT1-associated growth defects to occur, and ablating OAT1 caused a significant increase in acetate and other metabolites associated with anaerobic respiration. OAT1 increased the succinate dehydrogenase reaction rate by 35% in in vitro assays with physiological concentrations of both succinate and malate. Our results suggest that OAT1 is a universal metabolite repair enzyme that is required to maximize aerobic respiration efficiency by preventing succinate dehydrogenase inhibition.

Background: Working despite feeling ill – presenteeism – is a widespread behavioral phenomenon. Previous research has shown that presenteeism is influenced by various work-related and personal factors. It's an illness behavior leading to a range of negative but also positive consequences. Due to coronavirus disease 2019 (COVID-19) pandemic, remote work has become the “new normal” for many employees. But so far, little is known about presenteeism in remote work. This study aims to investigate presenteeism in remote work by looking at the extent of remote presenteeism, differences to presenteeism in on-site work, and associated factors. Methods: A nationwide cross-sectional online survey was conducted in Germany with N = 233 participants. Data were analyzed using descriptive statistics, t-tests, and correlation analysis. Results: The results reveal that presenteeism is prevalent in remote work x̅ = 4.13 days (Md = 3; D = 2; s = 4.95). A low ability to detach from work (r = -.17; p = .005) and low supervisor support (r = -.14; p = .02) is associated with more remote presenteeism days. Remote working conditions seem to facilitate presenteeism. Conclusion: This study provides empirical insights into a subject area of great societal relevance. The results show that awareness should be raised for presenteeism in remote work. It should be regarded as a behavior that can be functional or dysfunctional, depending on the individual situation. Supervisor support and detachment should be fostered to help reduce dysfunctional presenteeism. Promotion of health literacy might help remote workers to decide on a health-oriented illness behavior. Further research is vital to analyze to what extent and under which circumstances presenteeism in remote work is (dys)functional and to derive clear recommendations.

Chemical sensors, relying on changes in the electrical conductance of a gas-sensitive material due to the surrounding gas, typically react with multiple target gases and the resulting response is not specific for a certain analyte species. The purpose of this study was the development of a multi-sensor platform for systematic screening of gas-sensitive nanomaterials. We have developed a specific Si-based platform chip, which integrates a total of 16 sensor structures. Along with a newly developed measurement setup, this multi-sensor platform enables simultaneous performance characterization of up to 16 different sensor materials in parallel in an automated gas measurement setup. In this study, we chose the well-established ultrathin SnO2 films as base material. In order to screen the sensor performance towards type and areal density of nanoparticles on the SnO2 films, the films are functionalized by ESJET printing Au-, NiPt-, and Pd-nanoparticle solutions with five different concentrations. The functionalized sensors have been tested toward the target gases: carbon monoxide and a specific hydrogen carbon gas mixture of acetylene, ethane, ethne, and propene. The measurements have been performed in three different humidity conditions (25%, 50% and 75% r.h.). We have found that all investigated types of NPs (except Pd) increase the responses of the sensors towards CO and HCmix and reach a maximum for an NP type specific concentration.

India’s biometric unique ID Aadhaar has been at the forefront of the global revolution in digital identification, and India’s most significant investment in state capacity over the past decade. Yet, its application to social protection programs has been controversial. Proponents claim that the use of Aadhaar to identify and authenticate beneficiaries in these programs has led to considerable fiscal savings, while critics claim that it has led to denial of benefits to the marginalized and caused substantial harm. We review research on the use and impact of Aadhaar in social programs in India over the last decade. Our main takeaway from the review is that biometric authentication has reduced leakage in multiple settings, but its impact on beneficiaries depends crucially on the protocols and details of implementation. We conclude with a list of policy suggestions for obtaining the benefits of Aadhaar while minimizing the risk of harm to beneficiaries.