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  1. Article ; Online: Referral practices of recent graduate and experienced physiotherapists working in Australian primary care for people with musculoskeletal conditions.

    Macpherson, S / Rebbeck, T R / Coates, S / Evans, K

    Musculoskeletal science & practice

    2023  Volume 64, Page(s) 102745

    Abstract: Background: People with musculoskeletal conditions often seek care from physiotherapists. Some, particularly those at risk of poor outcomes, may benefit from referral to physiotherapists with expertise in managing musculoskeletal conditions and/or ... ...

    Abstract Background: People with musculoskeletal conditions often seek care from physiotherapists. Some, particularly those at risk of poor outcomes, may benefit from referral to physiotherapists with expertise in managing musculoskeletal conditions and/or multidisciplinary care. Understanding referral practices of physiotherapists, and how experience influences those practices, may assist in implementing optimal care pathways in primary care.
    Aims: Explore (i) current referral practices of recent graduate and experienced physiotherapists who manage musculoskeletal conditions; (ii) opinions about referral to specialist physiotherapists for people at risk of poor outcomes.
    Methods: This qualitative study consisted of 23 semi-structured interviews with recent graduate (n = 9) and experienced physiotherapists (n = 14) working in primary care. Perspectives of participants' current referral practices (to whom, when and why they are referred) and referral to specialist physiotherapists were sought. Interviews were recorded and transcribed verbatim prior to analysis.
    Results: Referral practices for both groups were influenced by specific diagnoses, complexity of presentations, confidence, self-awareness, the clinical environment and system-related factors. Experienced physiotherapists were more confident and specific in their referrals and had established trusted networks compared with new graduates. Early referral to specialist physiotherapists was more likely when therapists were co-located. Barriers to early referral were lack of awareness, health system factors and impact on the patient (e.g., financial, time, continuity of care).
    Conclusion: Understanding factors influencing referral decisions may improve both intra- and interprofessional care for people with musculoskeletal conditions. Referral of people at risk of poor outcomes to specialist physiotherapists may be improved by greater intraprofessional awareness and clarity of roles.
    MeSH term(s) Humans ; Referral and Consultation ; Physical Therapists ; Musculoskeletal Diseases/therapy ; Australia ; Qualitative Research ; Primary Health Care
    Language English
    Publishing date 2023-03-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2888772-4
    ISSN 2468-7812
    ISSN (online) 2468-7812
    DOI 10.1016/j.msksp.2023.102745
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The rising burden of cancer in low- and middle-Human Development Index countries.

    Fadelu, Temidayo / Rebbeck, Timothy R

    Cancer

    2021  Volume 127, Issue 16, Page(s) 2864–2866

    MeSH term(s) Developing Countries ; Humans ; Neoplasms/epidemiology
    Language English
    Publishing date 2021-06-04
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.33586
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State.

    Svensson, Bengt / Nitu, Florentin R / Rebbeck, Robyn T / McGurran, Lindsey M / Oda, Tetsuro / Thomas, David D / Bers, Donald M / Cornea, Razvan L

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... ...

    Abstract Ca
    Language English
    Publishing date 2023-07-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.07.548138
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State.

    Svensson, Bengt / Nitu, Florentin R / Rebbeck, Robyn T / McGurran, Lindsey M / Oda, Tetsuro / Thomas, David D / Bers, Donald M / Cornea, Razvan L

    International journal of molecular sciences

    2023  Volume 24, Issue 16

    Abstract: ... ...

    Abstract Ca
    MeSH term(s) Binding Sites ; Drug Delivery Systems ; Fluorescence Resonance Energy Transfer ; Ryanodine Receptor Calcium Release Channel
    Chemical Substances Ryanodine Receptor Calcium Release Channel
    Language English
    Publishing date 2023-08-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241612547
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Germline Testing Around the Globe: Challenges in Different Practice Settings.

    Al-Sukhun, Sana / Masannat, Yazan / Wegman-Ostrosky, Talia / Shrikhande, Shailesh V / Manirakiza, Achille / Fadelu, Temidayo / Rebbeck, Timothy R

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2023  Volume 43, Page(s) e390522

    Abstract: Cancer is an increasing global public health burden. Lately, more emphasis has emerged on the importance of heredity in cancer, mostly driven by the introduction of germline genetic variants-directed therapeutics. It is true that 40% of cancer risk is ... ...

    Abstract Cancer is an increasing global public health burden. Lately, more emphasis has emerged on the importance of heredity in cancer, mostly driven by the introduction of germline genetic variants-directed therapeutics. It is true that 40% of cancer risk is attributed to modifiable environmental and lifestyle factors; still, 16% of cancers could be heritable, accounting for 2.9 of the 18.1 million cases diagnosed worldwide. At least two third of those will be diagnosed in countries with limited resources-low- and middle-income countries, especially where high rates of consanguine marriage and early age at diagnosis are already prevalent. Both are hallmarks of hereditary cancer. This creates a new opportunity for prevention, early detection, and recently therapeutic intervention. However, this opportunity is challenged by many obstacles along the path to addressing germline testing in patients with cancer in the clinic worldwide. Global collaboration and expertise exchange are important to bridge the knowledge gap and facilitate practical implementation. Adapting existing guidelines and prioritization according to local resources are essential to address the unique needs and overcome the unique barriers of each society.
    MeSH term(s) Humans ; Germ Cells ; Life Style ; Public Health
    Language English
    Publishing date 2023-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2431126-1
    ISSN 1548-8756 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1548-8748
    DOI 10.1200/EDBK_390522
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Variant-specific Mendelian Risk Prediction Model.

    Bae, Eunchan / Dias, Julie-Alexia / Huang, Theodore / Chen, Jinbo / Parmigiani, Giovanni / Rebbeck, Timothy R / Braun, Danielle

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Many pathogenic sequence variants (PSVs) have been associated with increased risk of cancers. Mendelian risk prediction models use Mendelian laws of inheritance to predict the probability of having a PSV based on family history, as well as specified PSV ... ...

    Abstract Many pathogenic sequence variants (PSVs) have been associated with increased risk of cancers. Mendelian risk prediction models use Mendelian laws of inheritance to predict the probability of having a PSV based on family history, as well as specified PSV frequency and penetrance (agespecific probability of developing cancer given genotype). Most existing models assume penetrance is the same for any PSVs in a certain gene. However, for some genes (for example, BRCA1/2), cancer risk does vary by PSV. We propose an extension of Mendelian risk prediction models to relax the assumption that risk is the same for any PSVs in a certain gene by incorporating variant-specific penetrances and illustrating these extensions on two existing Mendelian risk prediction models, BRCAPRO and PanelPRO. Our proposed BRCAPRO-variant and PanelPRO-variant models incorporate variant-specific BRCA1/2 PSVs through the region classifications. Due to the sparsity of the variant information we classify BRCA1/2 PSVs into three regions; the breast cancer clustering region (BCCR), the ovarian cancer clustering region (OCCR), and an other region. Simulations were conducted to evaluate the performance of the proposed BRCAPRO-variant model compared to the existing BRCAPRO model which assumes the penetrance is the same for any PSVs in BRCA1 (and respectively BRCA2). Simulation results showed that the BRCAPRO-variant model was well calibrated to predict region-specific BRCA1/2 carrier status with high discrimination and accuracy on the region-specific level. In addition, we showed that the BRCAPRO-variant model achieved performance gains over the existing risk prediction models in terms of calibration without loss in discrimination and accuracy. We also evaluated the performance of the two proposed models, BRCAPRO-variant and PanelPRO-variant, on a cohort of 1,961 families from the Cancer Genetics Network (CGN). We showed that our proposed models provide region-specific PSV carrier probabilities with high accuracy, while the calibration, discrimination and accuracy of gene-specific PSV carrier probabilities were comparable to the existing gene-specific models. As more variant-specific PSV penetrances become available, we have shown that Mendelian risk prediction models can be extended to integrate the additional information, providing precise variant or region-specific PSV carrier probabilities and improving future cancer risk predictions.
    Language English
    Publishing date 2023-03-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.06.531363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Trends in mortality among Black and White men with prostate cancer in Massachusetts and Pennsylvania: Race and neighborhood socioeconomic position.

    Iyer, Hari S / Gomez, Scarlett L / Chen, Jarvis T / Trinh, Quoc-Dien / Rebbeck, Timothy R

    Cancer

    2021  Volume 127, Issue 14, Page(s) 2525–2534

    Abstract: Background: Reducing disparities in men with prostate cancer (PCa) that may be caused by racial and socioeconomic differences is a major public health priority. Few reports have studied whether these disparities have changed over time.: Methods: Men ... ...

    Abstract Background: Reducing disparities in men with prostate cancer (PCa) that may be caused by racial and socioeconomic differences is a major public health priority. Few reports have studied whether these disparities have changed over time.
    Methods: Men diagnosed with PCa from January 1, 2000 to December 31, 2015 were identified from the Massachusetts and Pennsylvania cancer registries. All-cause mortality and PCa and cardiovascular cause-specific mortality were assessed. To estimate neighborhood socioeconomic position (nSEP), a summary score was generated using census tract-level measures of income, wealth, educational attainment, and racial and income segregation. Participants were grouped by diagnosis year (2000-2003, 2004-2007, 2008-2011, or 2012-2015), and changing trends in the mortality rate ratio by race and nSEP were estimated using covariate-adjusted Cox models with follow-up for up to 10 years, until death, or until censoring on January 1, 2018.
    Results: There were 193,883 patients with PCa and 43,661 deaths over 1,404,131 person-years of follow-up. The Black-White adjusted hazard ratio (aHR) from 2000 to 2003 through 2012 to 2015 was stable for all-cause mortality (aHR, 1.14 to 0.97; P for heterogeneity = .42), decreased for PCa-specific mortality (aHR, 1.38 to 0.93; P for heterogeneity = .005), and increased for cardiovascular mortality (aHR, 1.09 to 1.28; P for heterogeneity = .034). The aHR comparing those in the lowest versus the highest nSEP quintile increased significantly for all-cause mortality (aHR, 1.54 to 1.79; P for heterogeneity = .008), but not for PCa-specific mortality (aHR, 1.60 to 1.72; P for heterogeneity = .40) or cardiovascular mortality (aHR, 1.72 to 1.89; P for heterogeneity = .085).
    Conclusions: Although Black-White disparities in prostate mortality declined in Massachusetts and Pennsylvania over the study period, nSEP mortality disparity trends were stagnant or increased, warranting further attention.
    Lay summary: Few reports have examined whether racial and socioeconomic disparities in prostate cancer mortality have widened or narrowed in recent years. Using data from 2 state registries (Massachusetts and Pennsylvania) with differing intensities of government-mandated health insurance, trends in racial and neighborhood socioeconomic disparities were studied among Black and White men diagnosed from 2000 to 2015. Overall, trends in racial disparities were stagnant for all-cause mortality, shrank for prostate mortality, and widened for cardiovascular mortality. Disparities associated with neighborhood socioeconomic status either were stagnant or widened across all mortality end points. In general, disparities were more pronounced in Pennsylvania than in Massachusetts.
    MeSH term(s) Black or African American ; Humans ; Male ; Pennsylvania/epidemiology ; Prostatic Neoplasms ; Social Class ; Socioeconomic Factors ; White People
    Language English
    Publishing date 2021-04-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.33506
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: ent

    Gochman, Aaron / Do, Tri Q / Kim, Kyungsoo / Schwarz, Jacob A / Thorpe, Madelaine P / Blackwell, Daniel J / Ritschel, Paxton A / Smith, Abigail N / Rebbeck, Robyn T / Akers, Wendell S / Cornea, Razvan L / Laver, Derek R / Johnston, Jeffrey N / Knollmann, Bjorn C

    Molecular pharmacology

    2024  Volume 105, Issue 3, Page(s) 194–201

    Abstract: Intracellular ... ...

    Abstract Intracellular Ca
    MeSH term(s) Mice ; Animals ; Anti-Arrhythmia Agents/pharmacology ; Anti-Arrhythmia Agents/therapeutic use ; Ryanodine Receptor Calcium Release Channel/genetics ; Ryanodine Receptor Calcium Release Channel/metabolism ; Arrhythmias, Cardiac/drug therapy ; Arrhythmias, Cardiac/metabolism ; Depsipeptides/metabolism ; Depsipeptides/therapeutic use ; Death, Sudden, Cardiac/etiology ; Biological Products ; Myocytes, Cardiac/metabolism ; Calcium/metabolism
    Chemical Substances Anti-Arrhythmia Agents ; Ryanodine Receptor Calcium Release Channel ; verticilide ; Depsipeptides ; Biological Products ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/molpharm.123.000752
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Prostate cancer age-standardised incidence increase between 2006 and 2016 in Gauteng Province, South Africa: A laboratory data-based analysis.

    Cassim, N / Ahmad, A / Wadee, R / Rebbeck, T R / Glencross, D K / George, J A

    South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde

    2020  Volume 111, Issue 1, Page(s) 26–32

    Abstract: Background: Prostate cancer (PCa) is the leading male neoplasm in South Africa (SA) and is the second most frequently diagnosed cancer among men globally. Age-specific incidence rates (ASIRs) vary by up to 189-fold globally, with an ASIR of 68.0 per 100 ...

    Abstract Background: Prostate cancer (PCa) is the leading male neoplasm in South Africa (SA) and is the second most frequently diagnosed cancer among men globally. Age-specific incidence rates (ASIRs) vary by up to 189-fold globally, with an ASIR of 68.0 per 100 000 in 2018 in SA.
    Objectives: To describe PCa among men undergoing prostate biopsy in Gauteng Province, SA.
    Methods: We undertook a retrospective descriptive study using prostate biopsy data collected from the National Health Laboratory Service (NHLS) database between 2006 and 2016. We extracted the Systematized Nomenclature of Medicine (SNOMED) clinical terms morphology and topography codes to assign histological findings using the International Classification of Diseases for Oncology. PCa was defined as adenocarcinoma with a reported Gleason Score (GS). The new grade group (GG) based on the GS is defined as follows; (i) GG1 for a GS ≤6; (ii) GG2 for a GS of 3 + 4 = 7

    (iii) GG3 for a GS of 4 + 3 = 7; (iv) GG4 for a GS of 8; and (v) GG5 for a GS ≥9. Higher-grade disease was defined as GG4 and GG5 (GS ≥8), in line with local guidelines. We reported associations of PCa with a GS ≥7 with age and race and used provincial and world standard population data to determine annual ASIRs.
    Results: We identified 22 937 biopsies referred to the NHLS between 2006 and 2016. Of the 6 448 biopsies (39%) with a PCa finding for black Africans, 46% were diagnosed with high-risk PCa compared with 36 - 40% for other race groups (p<0.0001). Black Africans were more likely than whites to have GG4 or GG5 PCa (odds ratio 1.45; 95% confidence interval 1.27 - 1.67). The ASIR increased from 44.9 per 100 000 in 2006 to 57.3 per 100 000 in 2016.
    Conclusions: Black African men were significantly more likely to present with PCa with a GS ≥8 (GG4 and GG5) compared with the other racial groups in Gauteng. The ASIR increased dramatically during the study period, perhaps as a result of increased screening and awareness. There is a need for additional research to better understand why black African men present with higher-grade disease.
    MeSH term(s) Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Biopsy ; Humans ; Incidence ; Laboratories ; Male ; Mass Screening/methods ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/epidemiology ; Prostatic Neoplasms/pathology ; Retrospective Studies ; South Africa/epidemiology
    Language English
    Publishing date 2020-12-14
    Publishing country South Africa
    Document type Journal Article
    ZDB-ID 390968-2
    ISSN 2078-5135 ; 0038-2469 ; 0256-9574
    ISSN (online) 2078-5135
    ISSN 0038-2469 ; 0256-9574
    DOI 10.7196/SAMJ.2020.v111i1.14850
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.

    Roopnarine, Osha / Yuen, Samantha L / Thompson, Andrew R / Roelike, Lauren N / Rebbeck, Robyn T / Bidwell, Philip A / Aldrich, Courtney C / Cornea, Razvan L / Thomas, David D

    bioRxiv : the preprint server for biology

    2023  

    Abstract: We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim ...

    Abstract We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim is to discover drug-like small-molecule activators that improve SERCA’s function for the treatment of heart failure. We have previously demonstrated the use of an intramolecular FRET biosensor, based on human SERCA2a, by screening a small validation library using novel microplate readers that can detect the fluorescence lifetime or emission spectrum with high speed, precision, and resolution. Here we report results from a 50,000-compound screen using the same biosensor, with hit compounds functionally evaluated using Ca
    Language English
    Publishing date 2023-02-22
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.22.529557
    Database MEDical Literature Analysis and Retrieval System OnLINE

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