The Island Earth Field Studio: A High School Summer Program on Polynesian Voyaging in Hawaii

The Island Earth Field Studio is a ten-day program for high school students to learn about Polynesian voyaging in Hawaii as a framework to understand non-Western knowledge systems. The program design is grounded in research on the historical significance of voyaging and informed by current literature on adolescent development and place-based pedagogy. To further refine the program, a needs assessment was conducted using a combination of surveys and interviews with parents and educators in the continental United States (mainland) as well as interviews with local partners in Hawaii. The assessment revealed that cultural learning and community building were viewed by potential mainland participants as the most beneficial elements of the program, and the focus on Polynesian voyaging made it stand out as a unique experience. Correspondingly, Hawaiian ground partners viewed the program as a worthy opportunity to share their mission of cultural and environmental sustainability. Based on recommendations from the needs assessment, the program will recruit a diverse cohort of students with strong interest in indigenous culture and sustainability. The travel program will begin on the island of Oahu, where students will get to know the natural environment, history, and cultural context of Hawaii. Then on Maui, a specific hands-on focus on voyaging integrated with exposure to a wider variety of Hawaiian community initiatives will lend both depth and breadth to students’ insights. As students gain knowledge and skills throughout the program, they will work together to develop ideas about how to use what they’ve learned to build stronger and more sustainable communities. This program design is intended to align with the mission of local partners while also allowing space for students to process their own growth as individuals and as a community of peers

Unexpected Test Results in a Patient with Multiple Myeloma

A 53-year-old male patient with an established diagnosis of IgG λ multiple myeloma was seen by a hematologist–oncologist in consultation from an outside hospital. He had previously received 1 cycle of chemotherapy treatment, but he was found to be intermittently noncompliant with his therapy. The patient reported occasional nosebleeds and fatigue. Except for a slightly cachectic appearance, the physical examination was unremarkable. Chemistry and hematology laboratory results are shown in Table 1. Serum protein electrophoresis revealed monoclonal paraproteinemia in high abundance marked by an intense band in the γ region. Immunofixation electrophoresis was not ordered at that time, but it was previously performed at another institution and was positive for IgG monoclonal protein. The attending pathologist noted the discrepancy between the presence of a monoclonal band by serum protein electrophoresis and the patient\u27s quantitative immunoglobulin measurements. Several additional suspicious test results were also noted

Mitogenomics and the genetic differentiation of contemporary <i>Balaena mysticetus</i> (Cetacea) from Svalbard

Full mitochondrial genomes were assembled for 12 recently sampled animals from the Svalbard bowhead whale (Balaena mysticetus) stock via high-throughput sequencing data, facilitating analysis of the demographic history of the population for the first time. The Svalbard population has retained noticeable amounts of mitochondrial genome diversity despite extreme historical harvest levels. Haplotype and nucleotide diversities were similar to those estimated earlier for other bowhead whale populations. The reconstructed demographic history was in accordance with a boom–bust scenario, combining a slight Pleistocene population growth 25 000–35 000 years ago and a Holocene decline. Employing a mutation rate of 3.418 × 10–8 substitutions per site per year, the time to the most recent common ancestor for the mitochondrial genomes of the contemporary Svalbard bowhead whales was estimated to be 68 782 (54 353–83 216) years before the present. Based on 370 bp fragments of the D-loop region, significant genetic differentiation was detected between all extant bowhead whale populations across the circumpolar Arctic. Thus, the Svalbard bowhead whales can be regarded as a population with its own genetic legacy

Trabecular architecture of the distal femur in extant hominids

Extant great apes are characterized by a wide range of locomotor, postural and manipulative behaviours that each require the limbs to be used in different ways. In addition to external bone morphology, comparative investigation of trabecular bone, which (re‐)models to reflect loads incurred during life, can provide novel insights into bone functional adaptation. Here, we use canonical holistic morphometric analysis (cHMA) to analyse the trabecular morphology in the distal femoral epiphysis of Homo sapiens (n = 26), Gorilla gorilla (n = 14), Pan troglodytes (n = 15) and Pongo sp. (n = 9). We test two predictions: (1) that differing locomotor behaviours will be reflected in differing trabecular architecture of the distal femur across Homo, Pan, Gorilla and Pongo; (2) that trabecular architecture will significantly differ between male and female Gorilla due to their different levels of arboreality but not between male and female Pan or Homo based on previous studies of locomotor behaviours. Results indicate that trabecular architecture differs among extant great apes based on their locomotor repertoires. The relative bone volume and degree of anisotropy patterns found reflect habitual use of extended knee postures during bipedalism in Homo, and habitual use of flexed knee posture during terrestrial and arboreal locomotion in Pan and Gorilla. Trabecular architecture in Pongo is consistent with a highly mobile knee joint that may vary in posture from extension to full flexion. Within Gorilla, trabecular architecture suggests a different loading of knee in extension/flexion between females and males, but no sex differences were found in Pan or Homo, supporting our predictions. Inter‐ and intra‐specific variation in trabecular architecture of distal femur provides a comparative context to interpret knee postures and, in turn, locomotor behaviours in fossil hominins

Regulatory feedback cycle of the insulin-degrading enzyme and the amyloid precursor protein intracellular domain: Implications for Alzheimer's disease

One of the major pathological hallmarks of Alzheimer´s disease (AD) is an accumulation of amyloid-β (Aβ) in brain tissue leading to formation of toxic oligomers and senile plaques. Under physiological conditions, a tightly balanced equilibrium between Aβ-production and -degradation is necessary to prevent pathological Aβ-accumulation. Here, we investigate the molecular mechanism how insulin-degrading enzyme (IDE), one of the major Aβ-degrading enzymes, is regulated and how amyloid precursor protein (APP) processing and Aβ-degradation is linked in a regulatory cycle to achieve this balance. In absence of Aβ-production caused by APP or Presenilin deficiency, IDE-mediated Aβ-degradation was decreased, accompanied by a decreased IDE activity, protein level, and expression. Similar results were obtained in cells only expressing a truncated APP, lacking the APP intracellular domain (AICD) suggesting that AICD promotes IDE expression. In return, APP overexpression mediated an increased IDE expression, comparable results were obtained with cells overexpressing C50, a truncated APP representing AICD. Beside these genetic approaches, also AICD peptide incubation and pharmacological inhibition of the γ-secretase preventing AICD production regulated IDE expression and promoter activity. By utilizing CRISPR/Cas9 APP and Presenilin knockout SH-SY5Y cells results were confirmed in a second cell line in addition to mouse embryonic fibroblasts. In vivo, IDE expression was decreased in mouse brains devoid of APP or AICD, which was in line with a significant correlation of APP expression level and IDE expression in human postmortem AD brains. Our results show a tight link between Aβ-production and Aβ-degradation forming a regulatory cycle in which AICD promotes Aβ-degradation via IDE and IDE itself limits its own production by degrading AICD

eHealth in Geriatric Rehabilitation: An International Survey of the Experiences and Needs of Healthcare Professionals.

While eHealth can help improve outcomes for older patients receiving geriatric rehabilitation, the implementation and integration of eHealth is often complex and time-consuming. To use eHealth effectively in geriatric rehabilitation, it is essential to understand the experiences and needs of healthcare professionals. In this international multicentre cross-sectional study, we used a web-based survey to explore the use, benefits, feasibility and usability of eHealth in geriatric rehabilitation settings, together with the needs of working healthcare professionals. Descriptive statistics were used to summarize quantitative findings. The survey was completed by 513 healthcare professionals from 16 countries. Over half had experience with eHealth, although very few (52 of 263 = 20%) integrated eHealth into daily practice. Important barriers to the use or implementation of eHealth included insufficient resources, lack of an organization-wide implementation strategy and lack of knowledge. Professionals felt that eHealth is more complex for patients than for themselves, and also expressed a need for reliable information concerning available eHealth interventions and their applications. While eHealth has clear benefits, important barriers hinder successful implementation and integration into healthcare. Tailored implementation strategies and reliable information on effective eHealth applications are needed to overcome these barriers

Developing search strategies for clinical practice guidelines in SUMSearch and Google Scholar and assessing their retrieval performance

<p>Abstract</p> <p>Background</p> <p>Information overload, increasing time constraints, and inappropriate search strategies complicate the detection of clinical practice guidelines (CPGs). The aim of this study was to provide clinicians with recommendations for search strategies to efficiently identify relevant CPGs in SUMSearch and Google Scholar.</p> <p>Methods</p> <p>We compared the retrieval efficiency (retrieval performance) of search strategies to identify CPGs in SUMSearch and Google Scholar. For this purpose, a two-term GLAD (GuideLine And Disease) strategy was developed, combining a defined CPG term with a specific disease term (MeSH term). We used three different CPG terms and nine MeSH terms for nine selected diseases to identify the most efficient GLAD strategy for each search engine. The retrievals for the nine diseases were pooled. To compare GLAD strategies, we used a manual review of all retrievals as a reference standard. The CPGs detected had to fulfil predefined criteria, e.g., the inclusion of therapeutic recommendations. Retrieval performance was evaluated by calculating so-called diagnostic parameters (sensitivity, specificity, and "Number Needed to Read" [NNR]) for search strategies.</p> <p>Results</p> <p>The search yielded a total of 2830 retrievals; 987 (34.9%) in Google Scholar and 1843 (65.1%) in SUMSearch. Altogether, we found 119 unique and relevant guidelines for nine diseases (reference standard). Overall, the GLAD strategies showed a better retrieval performance in SUMSearch than in Google Scholar. The performance pattern between search engines was similar: search strategies including the term "guideline" yielded the highest sensitivity (SUMSearch: 81.5%; Google Scholar: 31.9%), and search strategies including the term "practice guideline" yielded the highest specificity (SUMSearch: 89.5%; Google Scholar: 95.7%), and the lowest NNR (SUMSearch: 7.0; Google Scholar: 9.3).</p> <p>Conclusion</p> <p>SUMSearch is a useful tool to swiftly gain an overview of available CPGs. Its retrieval performance is superior to that of Google Scholar, where a search is more time consuming, as substantially more retrievals have to be reviewed to detect one relevant CPG. In both search engines, the CPG term "guideline" should be used to obtain a comprehensive overview of CPGs, and the term "practice guideline" should be used if a less time consuming approach for the detection of CPGs is desired.</p

Vignette studies of medical choice and judgement to study caregivers' medical decision behaviour: systematic review

BACKGROUND: Vignette studies of medical choice and judgement have gained popularity in the medical literature. Originally developed in mathematical psychology they can be used to evaluate physicians' behaviour in the setting of diagnostic testing or treatment decisions. We provide an overview of the use, objectives and methodology of these studies in the medical field. METHODS: Systematic review. We searched in electronic databases; reference lists of included studies. We included studies that examined medical decisions of physicians, nurses or medical students using cue weightings from answers to structured vignettes. Two reviewers scrutinized abstracts and examined full text copies of potentially eligible studies. The aim of the included studies, the type of clinical decision, the number of participants, some technical aspects, and the type of statistical analysis were extracted in duplicate and discrepancies were resolved by consensus. RESULTS: 30 reports published between 1983 and 2005 fulfilled the inclusion criteria. 22 studies (73%) reported on treatment decisions and 27 (90%) explored the variation of decisions among experts. Nine studies (30%) described differences in decisions between groups of caregivers and ten studies (33%) described the decision behaviour of only one group. Only six studies (20%) compared decision behaviour against an empirical reference of a correct decision. The median number of considered attributes was 6.5 (IQR 4-9), the median number of vignettes was 27 (IQR 16-40). In 17 studies, decision makers had to rate the relative importance of a given vignette; in six studies they had to assign a probability to each vignette. Only ten studies (33%) applied a statistical procedure to account for correlated data. CONCLUSION: Various studies of medical choice and judgement have been performed to depict weightings of the value of clinical information from answers to structured vignettes of care givers. We found that the design and analysis methods used in current applications vary considerably and could be improved in a large number of cases

Suppression of p75 Neurotrophin Receptor Surface Expression with Intrabodies Influences Bcl-xL mRNA Expression and Neurite Outgrowth in PC12 Cells

Background: Although p75 neurotrophin receptor (p75NTR) is the first neurotrophin receptor isolated, its diverse physiological functions and signaling have remained elusive for many years. Loss-of-function phenotypic analyses for p75NTR were mainly focused at the genetic level; however these approaches were impacted by off-target effect, insufficient stability, unspecific stress response or alternative active splicing products. In this study, p75NTR surface expression was suppressed for the first time at the protein level by endoplasmic reticulum (ER) retained intrabodies. Results: Three monoclonal recombinant antibody fragments (scFv) with affinities in the low nanomolar range to murine p75NTR were isolated by antibody phage display. To suppress p75NTR cell surface expression, the encoding genes of these scFvs extended by the ER retention peptide KDEL were transiently transfected into the neuron-like rat pheochromocytoma cell line PC12 and the mouse neuroblastoma x mouse spinal cord hybrid cell line NSC19. The ER retained intrabody construct, SH325-G7-KDEL, mediated a downregulation of p75NTR cell surface expression as shown by flow cytometry. This effect was maintained over a period of at least eight days without activating an unfolded protein response (UPR). Moreover, the ER retention of p75NTR resulted in downregulation of mRNA levels of the anti-apoptotic protein Bcl-xL as well as in strong inhibition of NGF-induced neurite outgrowth in PC12 cells. Conclusion: The ER retained intrabody SH325-G7-KDEL not only induces phenotypic knockdown of this p75NTR but als

The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer

hMena and the epithelial specific isoform hMena11a are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena11a expression and phosphorylates hMena11a, suggesting cross-talk between the ErbB receptor family and hMena/hMena11a in breast cancer. The aim of this study was to determine whether the hMena/hMena11a overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena11a expression and hMena11a phosphorylation. On the other hand, hMena/hMena11a knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena11a knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena11a as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients