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Abstract Developing microphysiological cell culture platforms with a three-dimensional (3D) microenvironment has been a significant advancement from traditional monolayer cultures. Still, most of the current microphysiological platforms are limited in closed designs, i.e. are not accessible after 3D cell culture loading. Here, we report an open-top microfluidic chip which enables the generation of two sequentially loaded 3D cell cultures without physical barriers restricting the nurture, gas exchange and cellular communication. As a proof-of-concept, we demonstrated the formation of two 3D vasculatures, one in the upper and the other in the lower compartment, under three distinct flow conditions: asymmetric side-to-center, symmetric side-to-center and symmetric center-to-side. We used computational modelling to characterize initial flow pressures in cell culture compartments. We showed prominent vessel formation and branched vasculatures in upper and lower cell culture compartments with interconnecting, lumenized vessels with in vivo-relevant diameter in all flow conditions. With advanced image processing, we quantified and compared the overall vascular network volume and the total length formed in asymmetric side-to-center, symmetric side-to-center and symmetric center-to-side flow conditions. Our results indicate that the developed chip can house two distinct 3D cell cultures with merging vessels between compartments and by providing asymmetric side-to-center or symmetric center-to-side flow vascular morphogenesis is enhanced in terms of overall network length. The developed open-top microfluidic chip may find various applications in generation of tissue-specific 3D-3D co-cultures for studying cellular interactions in vascularized tissues and organs.

Abstract Drainage and deforestation of tropical peat swamp forests (PSF) in Southeast Asia cause carbon emissions and biodiversity loss of global concern. Restoration efforts to mitigate these impacts usually involve peatland rewetting by blocking canals. However, there have been no studies to date of the optimal rewetting approach that will reduce carbon emission whilst also promoting PSF regeneration. Here we present results of a large-scale restoration trial in Sumatra (Indonesia), monitored for 7.5 years. Water levels in a former plantation were raised over an area of 4800 ha by constructing 257 compacted peat dams in canals. We find peat surface subsidence rates in the rewetted restoration area and adjoining PSF to be halved where water tables were raised from ~ − 0.6 m to ~ − 0.3 m, demonstrating the success of rewetting in reducing carbon emission. A total of 57 native PSF tree species were found to spontaneously grow in the most rewetted conditions and in high densities, indicating that forest regrowth is underway. Based on our findings we propose that an effective PSF restoration strategy should follow stepwise rewetting to achieve substantial carbon emission reduction alongside unassisted regrowth of PSF, thereby enabling the peat, forest and canal vegetation to establish a new nature-based ecosystem balance.

Abstract Heart failure (HF) is a major burden worldwide, and new therapies are urgently needed. Gene therapy is a promising new approach to treat myocardial diseases. However, current cardiac gene delivery methods for producing global myocardial effects have been inefficient. The aim of this study was to develop an endovascular, reproducible, and clinically applicable gene transfer method for global left ventricular (LV) transduction. Domestic pigs (n = 52) were used for the experiments. Global LV myocardium coverage was achieved by three retrograde injections into the three main LV vein branches. The distribution outcome was significantly improved by simultaneous transient occlusions of the corresponding coronary arteries and the main anastomotic veins of the retroinjected veins. The achieved cardiac distribution was visualized first by administering Indian Ink solution. Secondly, AdLacZ (2 × 1012vp) and AAV2-GFP (2 × 1013vg) gene transfers were performed to study gene transduction efficacy of the method. By retrograde injections with simultaneous coronary arterial occlusions, both adenovirus (Ad) and adeno-associated virus (AAV) vectors were shown to deliver an efficient transduction of the LV. We conclude that retrograde injections into the three main LV veins is a potential new approach for a global LV gene transfer.

Abstract Periplasmic solute-binding proteins (SBPs) specific for chitooligosaccharides, (GlcNAc)n (n = 2, 3, 4, 5 and 6), are involved in the uptake of chitinous nutrients and the negative control of chitin signal transduction in Vibrios. Most translocation processes by SBPs across the inner membrane have been explained thus far by two-domain open/closed mechanism. Here we propose three-domain mechanism of the (GlcNAc)n translocation based on experiments using a recombinant VcCBP, SBP specific for (GlcNAc)n from Vibrio cholerae. X-ray crystal structures of unliganded or (GlcNAc)3-liganded VcCBP solved at 1.2–1.6 Å revealed three distinct domains, the Upper1, Upper2 and Lower domains for this protein. Molecular dynamics simulation indicated that the motions of the three domains are independent and that in the (GlcNAc)3-liganded state the Upper2/Lower interface fluctuated more intensively, compared to the Upper1/Lower interface. The Upper1/Lower interface bound two GlcNAc residues tightly, while the Upper2/Lower interface appeared to loosen and release the bound sugar molecule. The three-domain mechanism proposed here was fully supported by binding data obtained by thermal unfolding experiments and ITC, and may be applicable to other translocation systems involving SBPs belonging to the same cluster.

Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. Methods The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. Discussion OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of “damage control”; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. Trial registration: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Abstract Background Alzheimer’s disease (AD) is a major determinant of healthcare costs and increase in the healthcare service use occur already before the AD diagnosis. However, little is known how the different diagnosis categories contribute to this increase in healthcare use. We investigated how the hospitalizations and specialized healthcare outpatient visits from different diagnosis categories, based on the International Classification of Diseases (ICD-10) chapters, contribute to increased specialized healthcare service use during ten-year period preceding AD diagnosis. Methods A register-based nationwide cohort of 42,934 community-dwelling persons who received clinically verified AD diagnosis in between 2008 and 2011 in Finland and 1:1 age, sex and hospital district- matched comparison cohort were included. Hospitalizations and specialized healthcare visits were categorized by the main diagnosis, according to the ICD-10 chapters. AD and dementia were separated to their own category. The number of persons with visits and stays was calculated for every 6 months, irrespective of the frequency of visits/stays individual had during that time window. Furthermore, the relative distribution of the diagnosis categories was computed. Results AD cohort was more likely to have visits and stays during the 10-year period (OR 1.19, 95% CI 1.17–1.21). The number of persons with visits and stays peaked in AD cohort from 1.5 years before the diagnosis when the differences in relative distribution of different diagnosis categories also became evident. The largest differences were observed for visits/stays with cognitive disorders, symptoms of unspecified diseases and psychiatric disorders diagnoses, and those with missing diagnosis codes in the last time window before AD diagnosis. Conclusions and implications Increased healthcare service use before AD diagnosis does not seem to arise from differences in specific diagnosis categories of ICD-10 such as diseases of the circulatory system, but from the higher frequency of visits and stays among persons with AD across diagnosis categories. Based on the relative distribution of diagnosis categories, the steep increase in healthcare service use just before and during the diagnostic process is likely due to prodromal symptoms and visits related to cognition.

Background: Social anxiety disorder (SAD) is one of the key mental health disorders of adolescence. Due to the mental health challenge across the globe in this age group, a growing acknowledgement of the need to effectively identify and treat incipient SAD at an early stage has been presented in many countries. Aim: The aim of this study was to examine the accuracy of detection of SAD in schools, using a detection toolkit and a professional operating model in which school psychologists acted in a consultant/coordinator role. The second aim was to gain initial data on usefulness and feasibility of brief, developmentally oriented cognitive therapy (DOCT-SAD) for adolescents with SAD. Methods: Ten adolescents, identified from upper secondary schools with a mean age of 13.8 years, participated in DOCT-SAD. Accuracy rate of detection in the school was calculated as the proportion of adolescents who had interview-confirmed SAD and completed the treatment out of those altogether referred from schools. Usefulness of DOCT-SAD was assessed with pre- post-treatment changes in symptoms of SAD (SPIN), mood (PHQ-9) and in adolescents’ wellbeing (YP-CORE), and by evaluating change in DSM-5 diagnostic status. Feasibility was evaluated by semi-structured interviews of adolescents and their parents. Results: Use of the SAD detection toolkit and the professional operating model yielded a 71% accuracy rate for schoolbased identification of adolescents who had SAD, and who eventually completed treatment. DOCT-SAD showed promise as treatment of SAD: adolescents’ symptoms of SAD and depression decreased markedly pre-post effect sizes being 1.6 and 1.4 respectively, adolescents’ wellbeing improved, and a 60% rate of diagnostic remission, comparable to established treatments, was found. Feasibility of DOCT-SAD appeared good or excellent for adolescents and parents. Discussion: As incidence of SAD is high in adolescence, methods for detection and treatment are needed. The 10-session DOCT-SAD shows promise for further development as a treatment for adolescent SAD. Conclusion: This case series found support for using a structured detection model, and for treatment of SAD using a brief cognitive therapy program among adolescents identified in the school.

IntroductionPeatlands are terrestrial-carbon hotspots, where changes in carbon pools and fluxes potentially caused by drying or warming may have significant feedbacks to climate change. In forested peatlands, fine-root biomass (FRB), and production (FRP) are important carbon pools and fluxes, but they and their depth distribution and plant functional type (PFT) composition are poorly known.MethodsWe studied the effects of persistent water-table level (WTL) drawdown on these characteristics in four forested boreal peatland site types that varied in soil nutrient and WTL regimes, ground vegetation and tree stand characteristics. Each site type was represented by a pair of one undrained and one drained site. Two pairs were nutrient-poor, Scots pine dominated sites, one very wet and one relatively dry in their undrained condition. The other two pairs were nutrient-rich, Norway spruce dominated sites, again one wetter and one drier in the undrained condition. FRB was estimated by separating and visually identifying roots from soil cores extending down to 50 cm depth. FRP was estimated using ingrowth cores covering the same depth, and the separated roots were identified using infrared spectroscopy.Results and discussionBoth FRB and FRP varied widely both within and among the different types of boreal forested peatland. In FRB, the clearest differences were seen in the two originally wettest sites, nutrient-poor tall-sedge pine fen and nutrient-rich herb-rich spruce swamp: FRB was smaller in the drained site compared to the undrained site in the pine fen, but the opposite was true in the spruce swamp. FRP was generally higher in the nutrient-poor, pine-dominated sites than the nutrient-rich, spruce-dominates sites. The depth distribution of FRB was more superficial than that of FRP, except for the most nutrient-rich spruce swamp. Tree and shrub roots dominated both FRB and FRP, except for the undrained pine fen, where graminoids and forbs dominated. Even there, these PFTs were replaced by trees and shrubs at the drained site. Site wetness and nutrient regime both thus clearly regulated FRB and FRP of the forested peatland site types studied, and both need to be considered when making any generalizations.

Abstract Background Type 2 diabetes is common in persons with Alzheimer’s disease (AD). Management of diabetes in persons with AD is challenging due to changing goals of care and susceptibility to adverse drug events including hypoglycemia. The aim of this study was to investigate the prevalence of diabetes drug use from 5 years before to 5 years after the time of AD diagnosis among persons with and without AD. Methods This was a nationwide register-based study of persons with and without AD and diabetes in Finland. We analyzed data from the Medication Use and Alzheimer’s disease (MEDALZ) study that included 70,718 community-dwelling people diagnosed with AD from 2005 to 2011. The study population included 8418 persons with AD and 6666 matched persons without AD who were diagnosed with diabetes 5 years before AD diagnosis (index date). We defined the prevalence of diabetes drug use in three-month evaluation periods from 5 years before until 5 years after the index date. Results Nearly all people with diabetes (94% in both cohorts) used one or more diabetes drugs on the index date. The most prevalent drug metformin was used by 60.9% of people with AD and 59.1% of people without AD. The next most prevalent drugs were sulfonylureas and insulin. The prevalence of diabetes drug use was similar in people with and without AD but began to decline 1 year after AD diagnosis in the AD cohort compared to non-AD cohort. Conclusions The decline in diabetes drug use after AD diagnosis may be attributed to clinicians and patients seeking to avoid serious adverse drug events including hypoglycemia. In addition, the findings may reflect personalized glycemic control and unintentional weight loss in persons with AD reducing the need for diabetes drugs.

Abstract Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119

Health care professionals are ageing, and there is a severe, global need to attract future employees. This study examines the construction of employer brand image among young health care professionals, and related elements. The qualitative research data were collected through email and personal interviews from young nursing and physician students. The analysis results indicate that organisations can affect their employer brand image for future employees through supportive working culture and human resource practices as well as direct marketing actions. The marketing and human resource practices targeted towards young health care professionals are underused. The results can help health care organisations in planning recruitment and marketing processes according to young health care professionals' expectations. This study integrates human resource management research and marketing research relating to employer branding and recruitment.

Opportunity identification is a continuous process in ecosystems. However, ambiguities and challenges associated with knowledge exploration and exploitation can retard opportunity recognition processes. This in turn may culminate in excessive expenditure of resources or loss of latent opportunities. The present study adopts an analytical approach and proposes a methodological roadmap that utilizes scientometric and text mining techniques. The roadmap uses data from Web of Science as input, and generates insights that support decision-making about resource saving, strategic planning, investment, and policymaking. Our roadmap extends methods used in studying ecosystems by combining existing and novel techniques in data analytics. Using Python and VOSViewer, we show an exemplary application of the new roadmap, framed in the context of the Nordic countries’ renewable energy ecosystem.

Abstract Tropical peatlands are among the most carbon‐dense ecosystems on Earth, and their water storage dynamics strongly control these carbon stocks. The hydrological functioning of tropical peatlands differs from that of northern peatlands, which has not yet been accounted for in global land surface models (LSMs). Here, we integrated tropical peat‐specific hydrology modules into a global LSM for the first time, by utilizing the peatland‐specific model structure adaptation (PEATCLSM) of the NASA Catchment Land Surface Model (CLSM). We developed literature‐based parameter sets for natural (PEATCLSMTrop,Nat) and drained (PEATCLSMTrop,Drain) tropical peatlands. Simulations with PEATCLSMTrop,Nat were compared against those with the default CLSM version and the northern version of PEATCLSM (PEATCLSMNorth,Nat) with tropical vegetation input. All simulations were forced with global meteorological reanalysis input data for the major tropical peatland regions in Central and South America, the Congo Basin, and Southeast Asia. The evaluation against a unique and extensive data set of in situ water level and eddy covariance‐derived evapotranspiration showed an overall improvement in bias and correlation compared to the default CLSM version. Over Southeast Asia, an additional simulation with PEATCLSMTrop,Drain was run to address the large fraction of drained tropical peatlands in this region. PEATCLSMTrop,Drain outperformed CLSM, PEATCLSMNorth,Nat, and PEATCLSMTrop,Nat over drained sites. Despite the overall improvements of PEATCLSMTrop,Nat over CLSM, there are strong differences in performance between the three study regions. We attribute these performance differences to regional differences in accuracy of meteorological forcing data, and differences in peatland hydrologic response that are not yet captured by our model.

The vasculature is an essential, physiological element in virtually all human tissues. Formation of perfusable vasculature is therefore crucial for reliable tissue modeling. Three-dimensional vascular networks can be formed through the co-culture of endothelial cells (ECs) with stromal cells embedded in hydrogel. Mesenchymal stem/stromal cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ASCs) are an attractive choice as stromal cells due to their natural perivascular localization and ability to support formation of mature and stable microvessels in vitro. So far, BMSCs and ASCs have been compared as vasculature-supporting cells in static cultures. In this study, BMSCs and ASCs were co-cultured with endothelial cells in a fibrin hydrogel in a perfusable microfluidic chip. We demonstrated that using MSCs of different origin resulted in vascular networks with distinct phenotypes. Both types of MSCs supported formation of mature and interconnected microvascular networks-on-a-chip. However, BMSCs induced formation of fully perfusable microvasculature with larger vessel area and length whereas ASCs resulted in partially perfusable microvascular networks. Immunostainings revealed that BMSCs outperformed ASCs in pericytic characteristics. Moreover, co-culture with BMSCs resulted in significantly higher expression levels of endothelial and pericyte-specific genes, as well as genes involved in vasculature maturation. Overall, our study provides valuable knowledge on the properties of MSCs as vasculature-supporting cells and highlights the importance of choosing the application-specific stromal cell source for vascularized organotypic models.

Collaborative project delivery models were introduced in North Sea oil and gas projects. Recently, they have been successfully applied in the context of construction and infrastructure projects but their application in industrial engineering project context has been limited. We analyze empirically which type of challenges there are in applying collaborative practices in two projects. The key challenges include the divergent objectives of the actors that hamper common goal setting; collaborative models and rewarding mechanisms which are perceived as inappropriate; the limited funding before investment decision when early involvement of key actors should be secured; the emphasis on collaboration capabilities with every actor which are not possible in tendering; and the collaboration with governmental authorities which needs a different approach from that with the other actors. Collaborative practices have a potential to improve project performance and identified challenges should be taken into account when implementing collaboration in industrial engineering projects.

Objective: We explored the effectiveness of preventive home visits on the health-related quality-of-life (HRQoL) and mortality among independently community-dwelling older adults. Design: A randomised controlled trial. Subjects: Independently home-dwelling older adults 75 years and older, consisting of 211 in the intervention and 211 in the control group. Setting: Hyvinkää town municipality, Finland. Main outcome measures: We used the change in HRQoL measured by the 15D scale as our primary outcome. Mortality at two years was retrieved from central registers. Results: At the one-year time point, the HRQoL according to the 15D scores deteriorated in the control group, whereas we found no change in the intervention group. The difference between the 15D score changes between the groups was −0.015 (95% CI −0.029 to −0.0016; p = 0.028, adjusted for age, sex, and baseline value). At the two-year time point as the visits ended, that difference diminished. There was no difference in mortality between the groups during the 24-month follow-up. Conclusion: Preventive home visits implemented by a multidisciplinary team with CGA appear to help slow down the decline in HRQoL among older adults, although the effect diminishes when the visits end.Key points We are exploring preventive home visits as means to support the health-related quality-of-life (HRQoL) of home-dwelling older adults Multiprofessional preventive home visits in this intervention study helped to maintain the HRQoL when measured using 15D The effects on HRQoL diminished when the intervention ended, so could further benefits be attained with a longer intervention?The clinical trial registration number: ACTRN12616001411437

Purpose This study aims to increase the understanding of digital platform businesses and business model innovation in two-sided markets. Design/methodology/approach A new business model canvas tool was created through abductive reasoning and a real-life case study. The case was a unique driving school digital platform that belongs to employee and professional service platforms. Findings The proposed business model canvas is based on Scholten’s canvas (2016) for platform businesses and complements it by acknowledging changes in people’s values and macro-environmental factors as new elements. Research limitations/implications (if applicable) The study is limited to an exemplary case of a driving school digital platform. However, the results and the novel canvas tool can be applied to innovating business models for digital service platforms in many industries. Originality/value The novelty of the study is derived from the insights created by the case study and the new tool that helps platform businesses innovate in two-sided markets. Keywords: digital business model; two-sided market; canvas; value proposition; values; PESTEL

Introduction CT is the primary imaging option for acute abdominal pain in adults. Intravenous (IV) contrast media use improves CT quality but may cause post-contrast acute kidney injury (PC-AKI). Retrospective studies show no association between reduced baseline renal function and IV contrast CT, but, to our knowledge, no data from randomised controlled trials exist.Methods and analysis The INCARO (INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn) trial is a multicentre, open-label, parallel group, superiority, individually randomised controlled trial comparing IV contrast-enhanced CT to native CT in patients requiring emergency abdominal or body CT with impaired renal function defined as an estimated glomerular filtration rate (eGFR) of 15 to 45 mL/min/1.73 m2. The primary outcome is a composite of all-cause mortality or renal replacement therapy (RRT) within 90 days from CT. Secondary outcomes are AKI measured by KDIGO (The Kidney Disease: Improving Global Outcomes) criteria within 72 hours from CT, organ dysfunction defined by mSOFA (modified Sequential Organ Failure Assessment) criteria after 48 hours from CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment. All-cause mortality, need for RRT and renal transplant in long-term follow-up are also measured. The calculated sample size is 994 patients. Patient recruitment is estimated to take 3 years.Ethics and dissemination The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.Trial registration number NCT04196244

As a result of changes in the local or regional business environment, small and medium-sized enterprises (SMEs) in many industries are facing the need to change their business models radically and seize new business opportunities or fall out of business. Although the important impact of SMEs in economic growth and job creation is well known, current knowledge is rather limited on the effects of competences for changing the business models in SMEs. This paper focuses on the links between SME competence changes and business model innovations in industrial structural changes in the external environment. The findings of a comparative case study of Russian and Finnish SMEs identified the positive attitude to change and activeness in external networking and in seeking new opportunities as enabling competences for business model innovation. The practical implications highlight the competence transformation strategies enabling business model innovation and the effects of different institutional environments.

Platelets are blood circulating corpuscles generated from megakaryocytes that initiate wound healing. Here, Moreau et al. describe a way of producing large quantities of megakaryocytes from human pluripotent stem cells in the laboratory, moving us a step closer to manufacturing transfusion products.

Three artists from New Mexico who identify as lesbian or queer create work that is informed by their life experiences. Their works show no literal explanations but depict symbolic resolutions. Who they are and what they have experienced have had a strong impact on their work. Through specific materials and distinct color palettes they share certain elements of their identities and experiences with viewers. It is the viewer's task to try and discover what the works are about and what each artist has communicated. This paper focuses on the lives and works of three contemporary artists from New Mexico. Two of these artists, Harmony Hammond and Helen Cozza, identify themselves as lesbian, and another, Erin Forrest, identifies herself as queer. Recognizing how an artist's identity can be symbolically or metaphorically conveyed in his or her work can help all students better understand how their own experience of life can inform their art. The author presents an art project that allows high school students to explore the works of the three contemporary artists, gaining insights into how life experiences frame artmaking choices and statements about their differences as well as their shared humanity. (Contains 5 figures and 3 endnotes.)

Helen Cozza is a contemporary artist living in New Mexico who began working as a painter and moved into printmaking. Prevalent in her work is the use of the grid and the patterns created by weaving. The imagery is reminiscent of the environmental deterioration that Cozza observed in Buffalo and Cleveland where she lived for many years. Cozza knew at a young age that she was a lesbian and her work clearly speaks to her identity. Her work demands close inspection to see the marks of difference beneath the surface. (Contains 5 images.)

Harmony Hammond, known both nationally and internationally, is a contemporary lesbian artist from New Mexico who has lectured and published extensively on feminist art, lesbian art, and the cultural representation of "difference." "Radiant Affection" is representative of Hammond's organic work from the early 1980s that makes present the gendered body. Despite a demanding schedule, Hammond continues to be involved and supportive of the lesbian and gay communities and has curated several art exhibitions of contemporary works by lesbian, gay, bisexual, transgendered, and two-spirited people. (Contains 3 figures.)

Mammen is one of the most versatile and unusual artists of her time. She was born Gertrud Johanna Mammen on November 21, 1890 in Berlin, Germany. During the 1920s and 1930s, Mammen created vivid depictions of life in the booming metropolis of Berlin. She portrayed people of all walks of life, but her focus was on the "New Woman" in the Weimar Republic and her role in society. At the time, Berlin was the center for lesbian and gay subculture in Germany. Mammen painted a realistic picture of her female subjects, unabashedly depicting lesbians involved in intimate relationships--some portraits less obvious and more covert than others. This article offers a look at the life and works of Mammen. (Contains 1 note.)

In this paper, the author, who teaches a secondary arts method course at a southwestern university, describes how curriculum planning enabled her to introduce students to the art of lesbian and gay artists, thereby helping the students to understand what they can expect in the real world of teaching and what they might be up against should they decide to discuss issues that are important to them but may be seen as controversial. The lesson presentation helped students to learn about the components of a lesson plan while simultaneously observing an art lesson in action. The author believes that in order to teach well, preservice art teachers need to be aware of the components associated with curriculum planning, including the practicalities of art teaching and an awareness of real-world concerns. (Contains 7 endnotes.)

Provides a historical context on the issue of women dressing in clothing traditionally worn by men. Focuses on the lives, loves, and careers of Rosa Bonheur, Romaine Brooks, and Gluck (Hannah Gluckstein) who were artists who used clothing to express their sexual identity. (CMK)

Small RNA molecules, including microRNAs (miRNAs), play critical roles in regulating pluripotency, proliferation and differentiation of embryonic stem cells. miRNA-offset RNAs (moRNAs) are similar in length to miRNAs, align to miRNA precursor (pre-miRNA) loci and are therefore believed to derive from processing of the pre-miRNA hairpin sequence. Recent next generation sequencing (NGS) studies have reported the presence of moRNAs in human neurons and cancer cells and in several tissues in mouse, including pluripotent stem cells. In order to gain additional knowledge about human moRNAs and their putative development-related expression, we applied NGS of small RNAs in human embryonic stem cells (hESCs) and fibroblasts. We found that certain moRNA isoforms are notably expressed in hESCs from loci coding for stem cell-selective or cancer-related miRNA clusters. In contrast, we observed only sparse moRNAs in fibroblasts. Consistent with earlier findings, most of the observed moRNAs derived from conserved loci and their expression did not appear to correlate with the expression of the adjacent miRNAs. We provide here the first report of moRNAs in hESCs, and their expression profile in comparison to fibroblasts. Moreover, we expand the repertoire of hESC miRNAs. These findings provide an expansion on the known repertoire of small non-coding RNA contents in hESCs.

Nature Communications 7 Article number: 11208 (2016) Published 7 April 2016; Updated 28 July 2017 This Article contains an error in the author contributions section that has resulted in incorrect credit for preparation and critical analysis of the manuscript. The correct author contributions sectionis as follows: