Does gender influence leadership roles in academic surgery in the United States of America? A cross-sectional study.

BACKGROUND: Gender disparity remains prevalent in the field of academic surgery with an under-representation of women at senior leadership ranks. A wide variety of causes are reported to contribute to this gender-based discrimination but a current quantitative analysis in the US has significant importance. This cross-sectional study aims to document gender disparity in academic and leadership positions in surgery as well as its relationship with scholarly productivity. MATERIAL AND METHODS: The American Medical Association's Fellowship and Residency Electronic Interactive Database (FREIDA), was used to identify General Surgery programs. Each institution's website was used to identify its faculty's primary profiles for data collection. Individuals with an MD or DO, and an academic ranking of Professor, Associate Professor or Assistant Professor were included. Academic productivity was quantified by recording H-index, number of publications, number of citations, and years of active research of a physician. All statistical analysis was performed on SPSS Statistics version 20.0. RESULTS: A total of 144 academic programs were including in our analysis constituting 4085 surgeons, only one-fifth (n = 873, 21%) of which were women. Furthermore, only 19% of all leadership positions were assumed by female surgeons. Leadership positions and academic rank correlated significantly with increasing research productivity. The difference in H-index between genders was statistically significant (P < 0.05) with men possessing a higher median for H-index [13] than women [9]. Transplantation Surgery [17] had the highest median H-indices for female surgeons. Male surgeons (n = 18) were twice as likely to be Departmental Chairs as their female counterparts (n = 9). However, female surgical oncologists held the highest proportion of leadership positions (31%). CONCLUSION: A significant gender-based disparity was found in leadership positions and academic ranks. Research productivity appeared to be integral for academic and leadership appointments. Institution-level measures that enhance support, mentorship, and sponsorship for women are imperative to achieve overall parity in general surgery.

T1 characteristics of interstitial pulmonary fibrosis on 3T MRI-a predictor of early interstitial change?

BACKGROUND: Computed tomography (CT) is routinely used for diagnosis and characterisation of idiopathic pulmonary fibrosis (IPF). The technique however has limited sensitivity in detection and monitoring of early fibrotic changes. The aim of this study was to evaluate T1 characteristics in the radiologically diseased lung parenchyma in IPF patient compared to apparently normal parenchyma in both interstitial lung disease (ILD) patients and healthy volunteers and to investigate the feasibility of the technique in prediction of early fibrotic lung changes that may not be visible on CT. METHODS: Ten patients with IPF underwent high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) on the same day of attendance. 3T MRI was repeated in seven patients with IPF to test the reproducibility of results. The control group included healthy volunteers (n=10). A modified look-locker inversion-recovery (MOLLI) sequence (124×192 acquisition matrix; 8 mm slice) was performed during a 15-20 s breathhold in a single slice. The position of MR slice was pre-selected where there was CT evidence of normal and fibrotic lung. MOLLI imaging was performed prior to the contrast administration, and at 15, 25, 30 and 35 min post Gadolinium. The imaging data were then processed with a curve-fitting technique to estimate T1 values. T1 values of the apparent fibrotic and normal lung in IPF patients and normal lung were compared. RESULTS: Fibrotic lung had a higher pre-contrast T1 than either morphologically normal lung in ILD patients or control lung (P=0.02) in healthy volunteers (1309±123, 1069±71, and 1011±172 ms, respectively). Morphologically normal lung T1 and control lung T1 were not significantly different pre-contrast, however, at 10 min after administration of Gadolinium, control lung had a significantly shorter T1 than either fibrotic or morphologically normal lung (494±34, 670±63, and 619±41 ms, respectively; P=0.001). T1 for fibrotic lung continued to decrease until 20 min after contrast agent administration (P≤0.0001), whereas morphologically normal lung T1 did not significantly change after 10 min (P>0.3). This indicates delayed uptake of contrast agent in the fibrotic lung compared with morphologically normal lung. CONCLUSIONS: T1 mapping of patients with IPF at 3T is feasible and demonstrates a significant difference between fibrotic lung tissue and morphologically normal lung tissue both before Gadolinium administration and at 10 min delayed post-contrast images. The technique is able to evaluate early fibrosis in patients with apparently morphologically normal lung.

The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer.

Chromatin undergoes structural changes in response to extracellular and environmental signals. We observed changes in nuclear morphology in cancer tissue biopsied after chemotherapy and hypothesised that these DNA damage-induced changes are mediated by histone deacetylases (HDACs). Nuclear morphological changes in cell lines (PE01 and PE04 models) and a xenograft model (OV1002) were measured in response to platinum chemotherapy by image analysis of nuclear texture. HDAC2 expression increased in PEO1 cells treated with cisplatin at 24h, which was accompanied by increased expression of heterochromatin protein 1 (HP1). HDAC2 and HP1 expression were also increased after carboplatin treatment in the OV1002 carboplatin-sensitive xenograft model but not in the insensitive HOX424 model. Expression of DNA damage response pathways (pBRCA1, γH2AX, pATM, pATR) showed time-dependent changes after cisplatin treatment. HDAC2 knockdown by siRNA reduced HP1 expression, induced DNA double strand breaks (DSB) measured by γH2AX, and interfered with the activation of DNA damage response induced by cisplatin. Furthermore, HDAC2 depletion affected γH2AX foci formation, cell cycle distribution, and apoptosis triggered by cisplatin, and was additive to the inhibitory effect of cisplatin in cell lines. By inhibiting expression of HDAC2, reversible alterations in chromatin patterns during cisplatin treatment were observed. These results demonstrate quantifiable alterations in nuclear morphology after chemotherapy, and implicate HDAC2 in higher order chromatin changes and cellular DNA damage responses in ovarian cancer cells in vitro and in vivo.