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Article ; Online: Globalizing transit worker stress.

D Fleming, Mark

2024 Volume 30, Issue 4, Page(s) 330–345

Abstract: Health scientists have claimed that urban transit workers suffer from higher rates of stress-related disease than workers in most other occupations. This paper examines how a network of scientists and labor organizers constructed the problem of transit ... ...

Abstract	Health scientists have claimed that urban transit workers suffer from higher rates of stress-related disease than workers in most other occupations. This paper examines how a network of scientists and labor organizers constructed the problem of transit worker stress as a global phenomenon. According to study participants, transit workers worldwide are subject to a similar set of stress-related risks, which can serve as a basis for worker solidarity. This paper analyzes how the concept of stress has been used to identify pathogenic environments and considers anthropological claims that the concept often abstracts and depoliticizes harmful arrangements. The findings show that scientists and labor organizers use the stress concept to construct a figure of a universally at-risk transit worker that serves the ends of transnational labor organizing. At the same time, by focusing on the case of San Francisco's transit workers, this analysis shows that a persistent association between stress and 'hard work'-in both lay and scientific discourses-may block recognition of stress-related harms for transit workers who are accused of being lazy and overpaid.
MeSH term(s)	Humans ; Anthropology, Medical ; Occupations
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2026472-0
ISSN	1469-2910 ; 1364-8470
ISSN (online)	1469-2910
ISSN	1364-8470
DOI	10.1080/13648470.2023.2246265
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Article ; Online: Medical neutrality and structural competency in conflict zones: Israeli healthcare professionals' reaction to political violence.

Orr, Zvika / Fleming, Mark D

Global public health

2023 Volume 18, Issue 1, Page(s) 2171087

Abstract: ... ...

Abstract	ABSTRACT
MeSH term(s)	Humans ; Israel ; Violence ; Arabs ; Health Personnel ; Delivery of Health Care
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2234129-8
ISSN	1744-1706 ; 1744-1706
ISSN (online)	1744-1706
ISSN	1744-1706
DOI	10.1080/17441692.2023.2171087
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Article ; Online: Loss of the placental iron exporter ferroportin 1 causes embryonic demise in late-gestation mouse pregnancy.

Cao, Chang / Fleming, Mark D

Development (Cambridge, England)

2022 Volume 149, Issue 23

Abstract: Fetal development relies on adequate iron supply by the placenta. The placental syncytiotrophoblasts (SCTB) express high levels of iron transporters, including ferroportin1 (Fpn1). Whether they are essential in the placenta has not been tested directly, ... ...

Abstract	Fetal development relies on adequate iron supply by the placenta. The placental syncytiotrophoblasts (SCTB) express high levels of iron transporters, including ferroportin1 (Fpn1). Whether they are essential in the placenta has not been tested directly, mainly due to the lack of gene manipulation tools in SCTB. Here, we aimed to generate a SCTB-specific Cre mouse and use it to determine the role of placental Fpn1. Using CRISPR/Cas9 technology, we created a syncytin b (Synb) Cre line (SynbCre) targeting the fetal-facing SCTB layer in mouse placental labyrinth. SynbCre deleted Fpn1 in late gestation mouse placentas reliably with high efficiency. Embryos without placental Fpn1 were pale and runted, and died before birth. Fpn1 null placentas had reduced transferrin receptor expression, increased oxidative stress and detoxification responses, and accumulated ferritin in the SCTB instead of the fetal endothelium. In summary, we demonstrate that SynbCre is an effective and specific tool to investigate placental gene function in vivo. The loss of Fpn1 in late gestation mouse placenta is embryonically lethal, providing direct evidence for an essential role of Fpn1 in placental iron transport.
MeSH term(s)	Female ; Pregnancy ; Mice ; Animals ; Placenta ; Iron ; Parturition ; Cation Transport Proteins/genetics
Chemical Substances	Iron (E1UOL152H7) ; metal transporting protein 1 ; Cation Transport Proteins
Language	English
Publishing date	2022-12-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.201160
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Article ; Online: Localization and Kinetics of the Transferrin-Dependent Iron Transport Machinery in the Mouse Placenta.

Cao, Chang / Fleming, Mark D

Current developments in nutrition

2021 Volume 5, Issue 4, Page(s) nzab025

Abstract: The placenta transports iron to the fetus to support growth and development. Mice are commonly used to study placental iron transport. The subcellular locations of transferrin receptor and ferroportin 1 in iron-transporting cells in the mouse placenta ... ...

Abstract	The placenta transports iron to the fetus to support growth and development. Mice are commonly used to study placental iron transport. The subcellular locations of transferrin receptor and ferroportin 1 in iron-transporting cells in the mouse placenta have not been directly assessed. Using immunogold electron microscopy, we determined that transferrin receptor is concentrated on the intracellular vesicles in syncytiotrophoblast I while ferroportin 1 is on the basal membrane of syncytiotrophoblast II. Fluorescent imaging of maternally injected transferrin iron in the placentas collected at 6 time points postinjection (
Language	English
Publishing date	2021-03-17
Publishing country	United States
Document type	Journal Article
ISSN	2475-2991
ISSN (online)	2475-2991
DOI	10.1093/cdn/nzab025
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Article ; Online: Photoresponsive Small Molecule Inhibitors for the Remote Control of Enzyme Activity.

Laczi, Dóra / Johnstone, Mark D / Fleming, Cassandra L

Chemistry, an Asian journal

2022 Volume 17, Issue 11, Page(s) e202200200

Abstract: The development of new and effective therapeutics is reliant on the ability to study the underlying mechanisms of potential drug targets in live cells and multicellular systems. A persistent challenge in many drug development programmes is poor ... ...

Abstract	The development of new and effective therapeutics is reliant on the ability to study the underlying mechanisms of potential drug targets in live cells and multicellular systems. A persistent challenge in many drug development programmes is poor selectivity, which can obscure the mechanisms involved and lead to poorly understood modes of action. In efforts to improve our understanding of these complex processes, small molecule inhibitors have been developed in which their OFF/ON therapeutic activity can be toggled using light. Photopharmacology is devoted to using light to modulate drugs. Herein, we highlight the recent progress made towards the development of light-responsive small molecule inhibitors of selected enzymatic targets. Given the size of this field, literature from 2015 onwards has been reviewed.
Language	English
Publishing date	2022-04-21
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2233006-9
ISSN	1861-471X ; 1861-4728
ISSN (online)	1861-471X
ISSN	1861-4728
DOI	10.1002/asia.202200200
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Article ; Online: Biomedicine and the treatment of difference in a Jerusalem emergency department.

Orr, Zvika / Jackson, Levi / Alpert, Evan Avraham / Fleming, Mark D

Social science & medicine (1982)

2023 Volume 339, Page(s) 116345

Abstract: Biomedicine has played a key role in the dissemination of modern social norms, such as the emphasis on individual autonomy and the distinction between science and religion. This study examines the way the mostly-Jewish members of the medical staff at an ... ...

Abstract	Biomedicine has played a key role in the dissemination of modern social norms, such as the emphasis on individual autonomy and the distinction between science and religion. This study examines the way the mostly-Jewish members of the medical staff at an emergency department of a Jerusalem hospital perceive Jewish ultra-Orthodox and Arab patients' behaviors vis-à-vis the existing biomedical norms. We analyzed participants' perceptions in terms of the social constructs they reveal, their meanings, and their implications. Semi-structured in-depth interviews were conducted with 24 staff members and were analyzed using content analysis. The staff described challenges in treating Arab and ultra-Orthodox patients, which they related to both groups' embeddedness in traditional "cultures" and collective identities. According to the participants, in both cases, the patients' cultural affiliations constrained their sense of individual autonomy and rationality. However, in the comparative analysis, two differences emerged. First, while both groups were perceived to diverge from modern norms of individual autonomy, in the case of Arab patients, these characteristics were presented as disruptive and potentially threatening to the hospital staff. By contrast, in the case of ultra-Orthodox patients, adherence to traditional and collective values was more likely to be represented as a risk to the patient, rather than to the staff. Second, staff were more likely to provide accommodations for ultra-Orthodox patients than for Arab patients. These accommodations were often described in the frame of "cultural competency." We suggest that divergences in how staff understood and responded to perceived cultural differences of each group reflect unequal impacts of structural determinants of health, including of political conflict. We recommend moving beyond the conceptual framework of cultural competency to strengthen the staff's structural competency, cultural and structural humility, and critical consciousness.
MeSH term(s)	Humans ; Arabs ; Cultural Competency ; Jews ; Religion ; Israel
Language	English
Publishing date	2023-10-27
Publishing country	England
Document type	Journal Article
ZDB-ID	4766-1
ISSN	1873-5347 ; 0037-7856 ; 0277-9536
ISSN (online)	1873-5347
ISSN	0037-7856 ; 0277-9536
DOI	10.1016/j.socscimed.2023.116345
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Article ; Online: Organizational and community resilience for COVID-19 and beyond: Leveraging a system for health and social services integration.

Fleming, Mark D / Safaeinili, Nadia / Knox, Margae / Brewster, Amanda L

Health services research

2023 Volume 59 Suppl 1, Page(s) e14250

Abstract: Objective: To examine how a preexisting initiative to align health care, public health, and social services influenced COVID-19 pandemic response.: Data sources and study setting: In-depth interviews with administrators and frontline staff in health ... ...

Abstract	Objective: To examine how a preexisting initiative to align health care, public health, and social services influenced COVID-19 pandemic response. Data sources and study setting: In-depth interviews with administrators and frontline staff in health care, public health, and social services in Contra Costa County, California from October, 2020, to May, 2021. Study design: Qualitative, semi-structured interviews examined how COVID-19 response used resources developed for system alignment prior to the pandemic. Data collection: We interviewed 31 informants including 14 managers in public health, health care, or social services and 17 social needs case managers who coordinated services across these sectors on behalf of patients. An inductive-deductive qualitative coding approach was used to systematically identify recurrent themes. Principal findings: We identified four distinct components of the county's system alignment capabilities that supported COVID-19 response, including (1) an organizational culture of adaptability fostered through earlier system alignment efforts, which included the ability and willingness to rapidly implement new organizational processes, (2) trusting relationships among organizations based on prior, positive experiences of cross-sector collaboration, (3) capacity to monitor population health of historically marginalized community members, including information infrastructures, data analytics, and population monitoring and outreach, and (4) frontline staff with flexible skills to support health and social care who had built relationships with the highest risk community members. Conclusions: Prior investments in aligning systems provided unanticipated benefits for organizational and community resilience during the COVID-19 pandemic. Our results illustrate a pathway for investment in system alignment efforts that build capacity within organizations and relationships between organizations to enhance resilience to crisis. Our findings suggest the usefulness of an integrated concept of organizational and community resilience that understands the resilience of systems of care as a vital resource for community resilience during crisis.
MeSH term(s)	Humans ; COVID-19 ; Pandemics ; Resilience, Psychological ; Social Work ; Delivery of Health Care
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	410435-3
ISSN	1475-6773 ; 0017-9124
ISSN (online)	1475-6773
ISSN	0017-9124
DOI	10.1111/1475-6773.14250
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Article ; Online: Finding the (biomarker-defined) subgroup of patients who benefit from a novel therapy: No time for a game of hide and seek.

McShane, Lisa Meier / Rothmann, Mark D / Fleming, Thomas R

Clinical trials (London, England)

2023 Volume 20, Issue 4, Page(s) 341–350

Abstract: An important element of precision medicine is the ability to identify, for a specific therapy, those patients for whom benefits of that therapy meaningfully exceed the risks. To achieve this goal, treatment effect usually is examined across subgroups ... ...

Abstract	An important element of precision medicine is the ability to identify, for a specific therapy, those patients for whom benefits of that therapy meaningfully exceed the risks. To achieve this goal, treatment effect usually is examined across subgroups defined by a variety of factors, including demographic, clinical, or pathologic characteristics or by molecular attributes of patients or their disease. Frequently such subgroups are defined by the measurement of biomarkers. Even though such examination is necessary when pursuing this goal, the evaluation of treatment effect across a variety of subgroups is statistically fraught due to both the danger of inflated false-positive error rate from multiple testing and the inherent insensitivity to how treatment effects differ across subgroups.Pre-specification of subgroup analyses with appropriate control of false-positive (i.e. type I) error is recommended when possible. However, when subgroups are specified by biomarkers, which could be measured by different assays and might lack established interpretation criteria, such as cut-offs, it might not be possible to fully specify those subgroups at the time a new therapy is ready for definitive evaluation in a Phase 3 trial. In these situations, further refinement and evaluation of treatment effect in biomarker-defined subgroups might have to take place within the trial. A common scenario is that evidence suggests that treatment effect is a monotone function of a biomarker value, but optimal cut-offs for therapy decisions are not known. In this setting, hierarchical testing strategies are widely used, where testing is first conducted in a particular biomarker-positive subgroup and then is conducted in the expanded pool of biomarker-positive and biomarker-negative patients, with control for multiple testing. A serious limitation of this approach is the logical inconsistency of excluding the biomarker-negatives when evaluating effects in the biomarker-positives, yet allowing the biomarker-positives to drive the assessment of whether a conclusion of benefit could be extrapolated to the biomarker-negative subgroup.Examples from oncology and cardiology are described to illustrate the challenges and pitfalls. Recommendations are provided for statistically valid and logically consistent subgroup testing in these scenarios as alternatives to reliance on hierarchical testing alone, and approaches for exploratory assessment of continuous biomarkers as treatment effect modifiers are discussed.
MeSH term(s)	Humans ; Biomarkers ; Precision Medicine
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-04-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2138796-5
ISSN	1740-7753 ; 1740-7745
ISSN (online)	1740-7753
ISSN	1740-7745
DOI	10.1177/17407745231169692
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Article ; Online: Hereditary myopathies associated with hematological abnormalities.

Beecher, Grayson / Fleming, Mark D / Liewluck, Teerin

Muscle & nerve

2022 Volume 65, Issue 4, Page(s) 374–390

Abstract: The diagnostic evaluation of a patient with suspected hereditary muscle disease can be challenging. Clinicians rely largely on clinical history and examination features, with additional serological, electrodiagnostic, radiologic, histopathologic, and ... ...

Abstract	The diagnostic evaluation of a patient with suspected hereditary muscle disease can be challenging. Clinicians rely largely on clinical history and examination features, with additional serological, electrodiagnostic, radiologic, histopathologic, and genetic investigations assisting in definitive diagnosis. Hematological testing is inexpensive and widely available, but frequently overlooked in the hereditary myopathy evaluation. Hematological abnormalities are infrequently encountered in this setting; however, their presence provides a valuable clue, helps refine the differential diagnosis, tailors further investigation, and assists interpretation of variants of uncertain significance. A diverse spectrum of hematological abnormalities is associated with hereditary myopathies, including anemias, leukocyte abnormalities, and thrombocytopenia. Recurrent rhabdomyolysis in certain glycolytic enzymopathies co-occurs with hemolytic anemia, often chronic and mild in phosphofructokinase and phosphoglycerate kinase deficiencies, or acute and fever-associated in aldolase-A and triosephosphate isomerase deficiency. Sideroblastic anemia, commonly severe, accompanies congenital-to-childhood onset mitochondrial myopathies including Pearson marrow-pancreas syndrome and mitochondrial myopathy, lactic acidosis, and sideroblastic anemia phenotypes. Congenital megaloblastic macrocytic anemia and mitochondrial dysfunction characterize SFXN4-related myopathy. Neutropenia, chronic or cyclical, with recurrent infections, infantile-to-childhood onset skeletal myopathy and cardiomyopathy are typical of Barth syndrome, while chronic neutropenia without infection occurs rarely in DNM2-centronuclear myopathy. Peripheral eosinophilia may accompany eosinophilic inflammation in recessive calpainopathy. Lipid accumulation in leukocytes on peripheral blood smear (Jordans' anomaly) is pathognomonic for neutral lipid storage diseases. Mild thrombocytopenia occurs in autosomal dominant, childhood-onset STIM1 tubular aggregate myopathy, STIM1 and ORAI1 deficiency syndromes, and GNE myopathy. Herein, we review these hereditary myopathies in which hematological features play a prominent role.
MeSH term(s)	Anemia, Sideroblastic/genetics ; Anemia, Sideroblastic/pathology ; Child ; Humans ; Lipid Metabolism, Inborn Errors ; Mitochondrial Diseases ; Mitochondrial Myopathies/genetics ; Mutation ; Myopathies, Structural, Congenital/genetics
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.27474
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Zs.A 1449: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Impact of Social Needs Case Management on Use of Medical and Behavioral Health Services: Secondary Analysis of a Randomized Controlled Trial.

Fleming, Mark D / Guo, Crystal / Knox, Margae / Brown, Daniel M / Hernandez, Elizabeth A / Brewster, Amanda L

Annals of internal medicine

2023 Volume 176, Issue 8, Page(s) 1139–1141

MeSH term(s)	Humans ; Case Management ; Health Services ; Quality of Life
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Randomized Controlled Trial ; Research Support, U.S. Gov't, P.H.S. ; Letter
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M23-0876
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