Personalising veteran healthcare: recognising barriers to access for minority and under-represented groups of veterans.

Veterans are not a demographically homogenous group, yet minority groups continue to be under-represented in research and report feeling less able to access clinical services to seek support. While veteran-specific healthcare has responded to the needs of the majority, the success of veteran mental health services is contingent on serving the whole veteran population. Key to the personalisation of healthcare is the question of access and a need to address specific inequalities and barriers to help-seeking behaviour. In this paper, we explore the issues of access to veteran healthcare at three levels: those barriers common to all veterans; those common to all minority groups of veterans; and those relevant to specific minority groups of veterans. Stigma, military attitudes and culture (eg, stoicism), and access to services and professionals with veteran-specific knowledge are universal barriers across veteran groups. Minority groups report a heightening of these barriers, alongside being 'othered' in veteran care settings, a lack of representation of them or their experiences in service descriptions and advertising, a lack of professional cultural competencies on specific issue, and the veteran environment potentially being retraumatising. Finally, barriers specific to individual groups are discussed. Attending to these is essential in developing holistic approaches to personalised healthcare that meets the needs of all veterans.

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrom macroglobulinaemia.

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrom macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response. Sixty treatment-naïve WM patients were enroled into this phase II trial and randomised (2:1) to receive cyclophosphamide and rituximab with either bortezomib (BRC) or fludarabine (FCR). The primary objective was to assess the overall response rate (ORR) in eligible patients receiving BRC (N = 41). An ORR of 97.6% (95%CI:87.1-99.9) was observed; 27 (65.9%) patients remain alive without progression after 62.6 months median follow-up, with 2-, 3- and 5-year progression-free survival (PFS) rates of 92.7% (95%CI:79.0-97.6), 80.5% (95%CI:64.8-89.7) and 65.5% (95%CI:48.8-77.9). Persistent WM B-cells were demonstrable in 19/38 patients at the end of treatment (median 0.24%, range 0.02-11.2%). PFS was markedly longer in patients with BM B-cell depletion (<0.004%) compared to those who had persistent BM B-cells detectable at end of treatment (HR = 0.06, 95%CI:0.01-0.47, p < 0.001), and remained independently associated after adjusting for baseline risk stratification or investigator-assessed response. BRC is a tolerable, highly efficacious regimen for treatment-naïve WM patients. BM B-cell depletion is independently associated with patient outcomes.

Your Family Connects: A Theory-Based Intervention to Encourage Communication about Possible Inherited Cancer Risk among Ovarian Cancer Survivors and Close Relatives.

INTRODUCTION: Encouraging family communication about possible genetic risk has become among the most important avenues for achieving the full potential of genomic discovery for primary and secondary prevention. Yet, effective family-wide risk communication (i.e., conveying genetic risk status and its meaning for other family members) remains a critical gap in the field. We aim to describe the iterative process of developing a scalable population-based communication outreach intervention, Your Family Connects, to reach ovarian cancer survivors and close relatives to communicate the potential for inherited risk and to consider genetic counseling. METHODS: Relational-level theories (e.g., interdependence theory) suggest that interventions to promote family cancer risk communication will be most effective if they consider the qualities of specific relationships and activate motives to preserve the relationship. Informed by these theories, we collaborated with 14 citizen scientists (survivors of ovarian cancer or relatives) and collected 261 surveys and 39 structured interviews over 12 weeks of citizen science activities in 2020. RESULTS: The citizen science findings and consideration of relational-level theories informed the content and implementation of Your Family Connects (www.yourfamilyconnects.org). CS results showed survivors favor personal contact with close relatives, but relatives were open to alternative contact methods, such as through health professionals. Recognizing the need for varied approaches based on relationship dynamics, we implemented a relative contact menu to enable survivors identify at-risk relatives and provide multiple contact options (i.e., survivor contact, health professional contact, and delayed contact). In line with relational autonomy principles, we included pros and cons for each option, assisting survivors in choosing suitable contact methods for each relative. DISCUSSION: Our developed intervention represents a novel application of relational-level theories and partnership with citizen scientists to expand genetic services reach to increase the likelihood for fair distribution of cancer genomic advances. The Your Family Connects intervention as part of a randomized trial in collaboration with the Georgia Cancer Registry compared with standard outreach.

Improving oncology first-in-human and Window of opportunity informed consent forms through participant feedback.

BACKGROUND: Although patient advocates have developed templates for standard consent forms, evaluating patient preferences for first in human (FIH) and window of opportunity (Window) trial consent forms is critical due to their unique risks. FIH trials are the initial use of a novel compound in study participants. In contrast, Window trials give an investigational agent over a fixed duration to treatment naïve patients in the time between diagnosis and standard of care (SOC) surgery. Our goal was to determine the patient-preferred presentation of important information in consent forms for these trials. METHODS: The study consisted of two phases: (1) analyses of oncology FIH and Window consents; (2) interviews of trial participants. FIH consent forms were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH information); Window consents were analyzed for the location(s) of information stating the trial may delay SOC surgery (delay information). Participants were asked about their preferred placement of the information in their own trial's consent form. The location of information in the consent forms was compared to the participants' suggestions for placement. RESULTS: 34 [17 FIH; 17 Window] of 42(81%) cancer patients approached participated. 25 consents [20 FIH; 5 Window] were analyzed. 19/20 FIH consent forms included FIH information, and 4/5 Window consent forms included delay information. 19/20(95%) FIH consent forms contained FIH information in the risks section 12/17(71%) patients preferred the same. Fourteen (82%) patients wanted FIH information in the purpose, but only 5(25%) consents mentioned it there. 9/17(53%) Window patients preferred delay information to be located early in the consent, before the "Risks" section.  3/5(60%) consents did this. CONCLUSIONS: Designing consents that reflect patient preferences more accurately is essential for ethical informed consent; however, a one-size fits all approach will not accurately capture patient preferences. We found that preferences differed for FIH and Window trial consents, though for both, patients preferred key risk information early in the consent. Next steps include determining if FIH and Window consent templates improve understanding.

Therapeutic Misconception about Research Procedures: Does a Simple Information Chart Improve Understanding?

In phase I trials, some biospecimens are used both for research and patient care and some for research only. Some research participants have therapeutic misconception, assuming all biospecimens are for patient care. This study's aim was to test if a simple information chart would improve understanding of nontherapeutic research procedures. A two-arm study was conducted. Participants in the control group (C) were asked whether biospecimens were for their care, for research only, or for both. The experimental group (E) was asked the same questions but provided with a study-specific information chart labeling the purpose of each biospecimen. One hundred one patients were interviewed. In both arms, understanding that pretreatment blood draws were for patient care and research was moderate (49% for C and 62% for E). Understanding that posttreatment blood draws were for research only was significantly higher in the experimental arm (16% for C and 44% for E; p = 0.002). Providing a simple information chart may help alleviate this aspect of therapeutic misconception.

Applying citizen science to engage families affected by ovarian cancer in developing genetic service outreach strategies.

Citizen science (CS) approaches involving non-professional researchers (citizens) as research collaborators has been used infrequently in health promotion generally and specifically, in cancer prevention. Standardized CS approaches may be especially useful for developing communication interventions to encourage families to consider cancer genetic services. We engaged survivors of ovarian cancer and their close relatives as CS collaborators to collect and help interpret data to inform content for a website, printed invitation materials, and short-message reminders. We applied an implementation quality framework, and posed four research questions regarding the feasibility of CS: recruitment, data collection, data quality and evaluation of the experience. CS members were recruited through three networks: clinical sites, local and national cancer support organizations, and online ovarian cancer patient support groups. The professional research team operationalized theory-aligned CS tasks, five data collection options, question banks/scripts for creating surveys, structured interviews, online training and ongoing support from research coaches. 14 CS members agreed to the 12-week and 20-hour commitment for an honorarium. CS members opted to do both qualitative and quantitative assessments. CS members collected 261 surveys and 39 structured interviews. The largest number of surveys were collected for Task 1 (n = 102) to assess survivors' reactions to different possible options for motivating survivors to visit a study website; 77% of this data were complete (i.e., no missing values). Data collected for tasks 2, 3, 4, and 5 (e.g., assessment of survivors' and relatives' respective communication preferences) ranged from 10 to 58 surveys (80% to 84% completeness). All data were collected within the specified time frame. CSs reported 17 hours of work on average and regarded the experience positively. Our experience suggests that CS engagement is feasible, can yield comprehensive quantitative and qualitative data, and is achievable in a relatively a short timeline.

Videos improve patient understanding of chemotherapy terminology in a rural setting.

BACKGROUND: It is critical patients understand the terms used to describe oncology treatments; however, even basic chemotherapy terminology can be misunderstood. Rural communities tend to have especially low levels of health literacy compared with nonrural communities. To address low health literacy in rural communities, this study tested rural participants' understanding of previously developed educational chemotherapy videos that were designed for an underserved urban population. Participants were also asked for feedback to determine if the videos could be improved. METHODS: Fifty English-speaking patients who reside in counties classified as rural according to the Rural-Urban Continuum Code designations (RUCC 4-9) participated in the study. Participants were asked to define 6 chemotherapy terms before and after viewing a short, animated video explaining the term in English. Rates of correct and incorrect definitions provided by participants were also compared with previously published results from an urban cohort. RESULTS: All participants had statistically significantly higher rates of correct definitions for all 6 terms following the video intervention. Palliative chemotherapy understanding improved the most (10% correct prevideo and 76% postvideo intervention). For each video, the majority of participants (77%-92%) suggested no changes to the videos. CONCLUSION: Given the prevalence of low health literacy in rural communities, it is important to have effective educational interventions to improve the understanding of basic oncology-treatment terminology. This study found that short, educational videos, originally designed for an underserved urban population, can significantly improve understanding of commonly misunderstood chemotherapy terminology in a rural setting as well. LAY SUMMARY: Chemotherapy terminology can be confusing to patients. Understanding can be especially difficult in areas with low health literacy, such as underserved urban and rural communities. To address this concern, previously developed short, animated videos describing basic chemotherapy terminology were found to improve patient understanding in an underserved urban setting. In this study, the videos were tested in a rural population and their effectiveness was established. Participants in the rural setting were significantly more likely to correctly define all 6 tested terms after watching the videos. Educational tools for high-need populations are essential to ensure patients can understand the treatment they receive.

Reassessing the measurement and presence of therapeutic misconception in a phase 1 setting.

BACKGROUND: Therapeutic misconception (TM) refers to research subjects' failure to distinguish the goals of clinical research from standard personal care. TM has traditionally been determined by questioning the patient about the research study's purpose. Recent research, however, has questioned whether TM is as prevalent as reported due to discrepancies between patient/researcher interpretations of TM questions. The authors have created an interview tool receptive to these advancements to more accurately determine the prevalence of TM. METHODS: Patients were questioned about the trial's purpose as follows: 1) "Is the trial mostly intending to help research and gain knowledge?," 2) "Is it mostly intending to help you as a person?," or 3) "Don't know." Participants were then asked what they thought this question was asking: A) "What my own intentions are for participating," B) "What the official purpose of the research study is," or C) "Not sure." A patient exhibited TM by answering that the official trial purpose was to help him or her. RESULTS: Patients (n = 98) had a mean age of 60 years, were mostly White (64%), had a combined family annual income ≥$60,000 (61%), and 49% had a college degree. Twelve of 98 patients (12%) definitely exhibited TM. This was much lower than the author's original finding of 68% in a similar cohort. Twenty-four of 98 patients (24.5%) were unclear about what one or both questions were asking and could not be categorized. CONCLUSIONS: Previously, a patient was thought to have TM if they answered that the purpose of the trial was to benefit to him or her. An additional query about how patients interpreted that question revealed only 12% definitely had TM. LAY SUMMARY: Therapeutic misconception (TM) refers to research subjects' failure to distinguish the goals of clinical research from standard personal care. TM signals a basic misunderstanding of the purpose of clinical research, threatening valid informed consent to participate in clinical trials. TM has traditionally been determined by questioning patients about their research study's purpose. Recent research, however, has questioned whether TM is as prevalent due to discrepancies between patient/researcher interpretations of TM questions. By developing an interview-tool receptive to these advancements, we report a lower TM estimate in the phase 1 setting (12%) than we found previously in a similar cohort (68%).

Real-world tyrosine kinase inhibitor treatment pathways, monitoring patterns and responses in patients with chronic myeloid leukaemia in the United Kingdom: the UK TARGET CML study.

Management of chronic myeloid leukaemia (CML) has recently undergone dramatic changes, prompting the European LeukemiaNet (ELN) to issue recommendations in 2013; however, it remains unclear whether real-world CML management is consistent with these goals. We report results of UK TARGET CML, a retrospective observational study of 257 patients with chronic-phase CML who had been prescribed a first-line TKI between 2013 and 2017, most of whom received first-line imatinib (n = 203). Although 44% of patients required ≥1 change of TKI, these real-world data revealed that molecular assessments were frequently missed, 23% of patients with ELN-defined treatment failure did not switch TKI, and kinase domain mutation analysis was performed in only 49% of patients who switched TKI for resistance. Major molecular response (MMR; BCR-ABL1IS ≤0·1%) and deep molecular response (DMR; BCR-ABL1IS ≤0·01%) were observed in 50% and 29%, respectively, of patients treated with first-line imatinib, and 63% and 54%, respectively, receiving a second-generation TKI first line. MMR and DMR were also observed in 77% and 44% of evaluable patients with ≥13 months follow-up, receiving a second-generation TKI second line. We found little evidence that cardiovascular risk factors were considered during TKI management. These findings highlight key areas for improvement in providing optimal care to patients with CML.

Allocating Scarce Health Care Resources During Pandemics: Making the Case for Patients with Advanced and Metastatic Cancer.

The oncology community is concerned that patients with cancer will be unfairly classified in pandemic allocation guidance. Past guidance either excluded patients with metastatic cancer from consideration or categorized them as having a survival of less than 1 year. Given recent improvements in treatments, we recommend that the prognosis of an individual patient with cancer be determined with input from a cancer specialist or, if this is impractical, that the presence of active metastatic solid cancer or relapsed hematologic malignancy is graded as a major comorbidity, with a likelihood that survival will be less than 5 years; severe limitation in physical functioning (3 or 4 on the Eastern Cooperative Oncology Group performance status) would define a patient with advanced cancer as having a severe comorbidity, with a likelihood of less than 1 year of survival. Cancer may be the "Emperor of all Maladies," but it is no longer a certain death sentence.

Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions.

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient's opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research.

Resolving the Chemically Discrete Structure of Synthetic Borophene Polymorphs.

Atomically thin two-dimensional (2D) materials exhibit superlative properties dictated by their intralayer atomic structure, which is typically derived from a limited number of thermodynamically stable bulk layered crystals (e.g., graphene from graphite). The growth of entirely synthetic 2D crystals, those with no corresponding bulk allotrope, would circumvent this dependence upon bulk thermodynamics and substantially expand the phase space available for structure-property engineering of 2D materials. However, it remains unclear if synthetic 2D materials can exist as structurally and chemically distinct layers anchored by van der Waals (vdW) forces, as opposed to strongly bound adlayers. Here, we show that atomically thin sheets of boron (i.e., borophene) grown on the Ag(111) surface exhibit a vdW-like structure without a corresponding bulk allotrope. Using X-ray standing wave-excited X-ray photoelectron spectroscopy, the positions of boron in multiple chemical states are resolved with sub-angström spatial resolution, revealing that the borophene forms a single planar layer that is 2.4 Å above the unreconstructed Ag surface. Moreover, our results reveal that multiple borophene phases exhibit these characteristics, denoting a unique form of polymorphism consistent with recent predictions. This observation of synthetic borophene as chemically discrete from the growth substrate suggests that it is possible to engineer a much wider variety of 2D materials than those accessible through bulk layered crystal structures.

Clickable Microgel Scaffolds as Platforms for 3D Cell Encapsulation.

While microporous scaffolds are increasingly used for regenerative medicine and tissue repair applications, the most common techniques to fabricate these scaffolds use templating or top-down fabrication approaches. Cytocompatible bottom-up assembly methods afford the opportunity to assemble microporous systems in the presence of cells and create complex polymer-cell composite systems in situ. Here, microgel building blocks with clickable surface groups are synthesized for the bottom-up fabrication of porous cell-laden scaffolds. The facile nature of assembly allows for human mesenchymal stem cells to be incorporated throughout the porous scaffold. Particles are designed with mean diameters of ≈10 and 100 µm, and assembled to create varied microenvironments. The resulting pore sizes and their distribution significantly alter cell morphology and cytoskeletal formation. This microgel-based system provides numerous tunable properties that can be used to control multiple aspects of cellular growth and development, as well as providing the ability to recapitulate various biological interfaces.

Structural Features of PbS Nanocube Monolayers upon Treatment with Mono- and Dicarboxylic Acids and Thiols at a Liquid-Air Interface.

This paper describes the ordering of PbS nanocubes (NCs) within free-standing monolayers (suspended on acetonitrile), upon exchanging the native oleate ligands for a series of thiolate and carboxylate ligands at the liquid-air interface. Treatment with either carboxylic acids or thiols effectively decreases the inter-NC separation of nearest-neighbor particles without etching the NC surface. Dicarboxylic acids and dithiols bridge neighboring NCs with an interparticle separation that is consistent with fully extended, bridging ligands. Monocarboxylic acids and monothiols separate NCs by an amount governed by their length, with long-chain ligands showing significant intercalation. (1)H NMR spectroscopy shows carboxylic acids are more effective at replacing the native oleate than are thiols, which we ascribe to the lower pKa values of carboxylic acids. The fast exchange that occurs upon treatment with monocarboxylic acids kinetically traps the clusters of particles in nonclosed packed geometries, so monolayers treated with monocarboxylic acids are, on average, less ordered than those treated with monothiols. Ex situ electron microscopy and grazing incidence small-angle X-ray scattering (GISAXS) analyses of deposited films on Si/SiO2 substrates show that NCs exchanged with nonbridging ligands pack more efficiently at long length scales than do NCs exchanged with bridging ligands, due primarily to the creation of defects within the NC lattice in response to the rigidity of the bridging ligand.

Rotationally Commensurate Growth of MoS2 on Epitaxial Graphene.

Atomically thin MoS2/graphene heterostructures are promising candidates for nanoelectronic and optoelectronic technologies. Among different graphene substrates, epitaxial graphene (EG) on SiC provides several potential advantages for such heterostructures, including high electronic quality, tunable substrate coupling, wafer-scale processability, and crystalline ordering that can template commensurate growth. Exploiting these attributes, we demonstrate here the thickness-controlled van der Waals epitaxial growth of MoS2 on EG via chemical vapor deposition, giving rise to transfer-free synthesis of a two-dimensional heterostructure with registry between its constituent materials. The rotational commensurability observed between the MoS2 and EG is driven by the energetically favorable alignment of their respective lattices and results in nearly strain-free MoS2, as evidenced by synchrotron X-ray scattering and atomic-resolution scanning tunneling microscopy (STM). The electronic nature of the MoS2/EG heterostructure is elucidated with STM and scanning tunneling spectroscopy, which reveals bias-dependent apparent thickness, band bending, and a reduced band gap of ∼0.4 eV at the monolayer MoS2 edges.

Electronic and Mechanical Properties of Graphene-Germanium Interfaces Grown by Chemical Vapor Deposition.

Epitaxially oriented wafer-scale graphene grown directly on semiconducting Ge substrates is of high interest for both fundamental science and electronic device applications. To date, however, this material system remains relatively unexplored structurally and electronically, particularly at the atomic scale. To further understand the nature of the interface between graphene and Ge, we utilize ultrahigh vacuum scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) along with Raman and X-ray photoelectron spectroscopy to probe interfacial atomic structure and chemistry. STS reveals significant differences in electronic interactions between graphene and Ge(110)/Ge(111), which is consistent with a model of stronger interaction on Ge(110) leading to epitaxial growth. Raman spectra indicate that the graphene is considerably strained after growth, with more point-to-point variation on Ge(111). Furthermore, this native strain influences the atomic structure of the interface by inducing metastable and previously unobserved Ge surface reconstructions following annealing. These nonequilibrium reconstructions cover >90% of the surface and, in turn, modify both the electronic and mechanical properties of the graphene overlayer. Finally, graphene on Ge(001) represents the extreme strain case, where graphene drives the reorganization of the Ge surface into [107] facets. From this work, it is clear that the interaction between graphene and the underlying Ge is not only dependent on the substrate crystallographic orientation, but is also tunable and strongly related to the atomic reconfiguration of the graphene-Ge interface.

Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis.

Erythrocytosis can arise from deregulation of the erythropoietin (Epo) axis resulting from defects in the oxygen-sensing pathway. Epo synthesis is controlled by the hypoxia inducible factor (HIF) complex, composed of an alpha and a beta subunit. There are 2 main alpha subunits, HIF-1 alpha and HIF-2 alpha. Recently, a HIF-2 alpha Gly537Trp mutation was identified in a family with erythrocytosis. This raises the possibility of HIF2A mutations being associated with other cases of erythrocytosis. We now report a subsequent analysis of HIF2A in a cohort of 75 erythrocytosis patients and identify 4 additional patients with novel heterozygous Met535Val and Gly537Arg mutations. All patients presented at a young age with elevated serum Epo. Mutations at Gly-537 account for 4 of 5 HIF2A mutations associated with erythrocytosis. These findings support the importance of HIF-2 alpha in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis.