Phenolic Glycolipid Facilitates Mycobacterial Escape from Microbicidal Tissue-Resident Macrophages

Publication date: Available online 24 August 2017
Source:Immunity
Author(s): C.J. Cambier, Seónadh M. O'Leary, Mary P. O'Sullivan, Joseph Keane, Lalita Ramakrishnan
Mycobacterium tuberculosis (Mtb) enters the host in aerosol droplets deposited in lung alveoli, where the bacteria first encounter lung-resident alveolar macrophages. We studied the earliest mycobacterium-macrophage interactions in the optically transparent zebrafish. First-responding resident macrophages phagocytosed and eradicated infecting mycobacteria, suggesting that to establish a successful infection, mycobacteria must escape out of the initially infected resident macrophage into growth-permissive monocytes. We defined a critical role for mycobacterial membrane phenolic glycolipid (PGL) in engineering this transition. PGL activated the STING cytosolic sensing pathway in resident macrophages, inducing the production of the chemokine CCL2, which in turn recruited circulating CCR2⁺ monocytes toward infection. Transient fusion of infected macrophages with CCR2⁺ monocytes enabled bacterial transfer and subsequent dissemination, and interrupting this transfer so as to prolong mycobacterial sojourn in resident macrophages promoted clearing of infection. Human alveolar macrophages produced CCL2 in a PGL-dependent fashion following infection, arguing for the potential of PGL-blocking interventions or PGL-targeting vaccine strategies in the prevention of tuberculosis.Video Abstract

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Cambier et al. find that activation of the STING pathway in lung-resident microbicidal macrophages by the mycobacterial surface lipid PGL enables bacterial escape by inducing the recruitment of mycobacterium-permissive monocytes via the CCL2-CCR2 chemokine axis. Their findings reveal a relocation strategy that enables mycobacterial dissemination, and argue for the potential of interventions targeting PGL in the prevention of tuberculosis.


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Late Presentation of Popliteal Angiosarcoma After Previously Treated Popliteal Artery Aneurysm

Publication date: Available online 23 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): M. Cherchi, S. Camparini




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Arteriovenous Fistulae for Haemodialysis: A Systematic Review and Meta-analysis of Efficacy and Safety Outcomes

Publication date: Available online 23 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): L.C. Bylsma, S.M. Gage, H. Reichert, S.L.M. Dahl, J.H. Lawson
BackgroundArteriovenous fistulae are the currently recommended gold standard vascular access modality for haemodialysis because of their prolonged patency, improved durability, and low risk of infection for those that mature. However, notable disadvantages are observed in terms of protracted maturation time, associated high rates of catheter use, and substantial abandonment rates. The aim of this study was to quantitatively summarize the outcomes of fistula patency, infection, maturation, and abandonment published in the scientific literature.MethodsThis was a systematic review and meta-analyses of studies evaluating fistula outcomes. Literature searches were conducted in multiple databases to identify observational and interventional studies of mean fistula patency rates at 1 year, infection risk, maturation time, and abandonment. Digitisation software was used to simulate individual patient level data from Kaplan–Meier survival plots.ResultsOver 8000 studies were reviewed, and from these, 318 studies were included comprising 62,712 accesses. For fistulas the primary unassisted, primary assisted, and secondary patency rates at one year were 64%, 73% and 79% respectively, however not all fistulas reported as patent could be confirmed as being clinically useful for dialysis (i.e. functional patency). For fistulas that were reported as mature, mean time to maturation was 3.5 months, however only 26% of created fistulas were reported as mature at 6 months and 21% of fistulas were abandoned without use. Overall risk of infection in fistula patients was 4.1% and the overall rate per 100 access days was 0.018.ConclusionsReported fistula patency rates may overstate their potential clinical utility when time to maturation, maturation rate, abandonment and infection are considered. Protracted maturation times, abandonment and infection all have a significant impact on evaluating the clinical utility of fistula creation. A rigorous and consistent set of outcomes definitions for hemodialysis access are necessary to clarify factors contributing to fistula success and the clinical consequence of fistula failure.



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Mothers' loss of control over eating during pregnancy in relation to their infants' appetitive traits

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Rachel P. Kolko, Rachel H. Salk, Gina M. Sweeny, Marsha D. Marcus, Michele D. Levine




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Renal collision tumor composed of oncocytoma and mucinous tubular and spindle cell carcinoma: case report of an unprecedented entity

Publication date: Available online 24 August 2017
Source:Human Pathology
Author(s): Komal Arora, Ross Miller, Seema Mullick, Steven Shen, Alberto G. Ayala, Jae Y. Ro
Primary renal collision tumors composed of two histologically distinct components are rare with only isolated case reports in the medical literature. Oncocytoma is a benign renal neoplasm, which is thought to originate from distal tubular epithelial cells. Mucinous tubular and spindle cell carcinoma (MTSCC) of kidney is a rare, relatively recently described renal neoplasm that was first included in the 2004 World Health Organization RCC classification as a distinct entity. Current studies suggest the tumor originates from the proximal nephron, although it is still controversial. The presence of concurrent oncocytoma with conventional (clear cell) RCC, chromophobe RCC and papillary RCC has been previously described. However, the association of oncocytoma with MTSCC has not yet been reported to our knowledge. Herein, we report the first case of a renal collision tumor composed of oncocytoma and MTSCC.



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Postablation neuroma of the myometrium – a report of 5 cases

Publication date: Available online 24 August 2017
Source:Human Pathology
Author(s): Stewart F. Cramer, Debra S. Heller
When hysterectomy is performed for chronic pelvic pain, routine pathology examination often provides no explanation. However, analysis of small uterine nerves using immunostains may help to address this deficiency. Small uterine nerves tend to be sparse or absent in wide areas of normal myometrium. Some studies of uterine nerves have suggested that endometriosis, adenomyosis, and fibroids are not inherently painful, with increased small nerves in the inner uterine wall associated with the history of pelvic pain. Although such areas may appear normal on Hematoxylin and Eosin (H&E), we have found a subtle inner wall lesion termed inner myometrial elastosis, best detected with trichrome or elastic stains, which may be a reaction to microscopic tears of inner myometrium. Such tears may induce increased inner wall innervation via the generation of Nerve Growth Factor in granulation tissue. In the course of studying uterine nerves with immunostains, we found 5 cases with florid nerve proliferation, after deep endometrial ablation for abnormal uterine bleeding led to increased pelvic pain. We suggest that immunostains for postablation neuromas should be done in hysterectomies when pelvic pain increases after endometrial ablation. This may offer gynecologists and their patients an objective finding with a rational, scientific explanation for the pelvic pain.



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Ring Chromosome in Myeloid Neoplasms is Associated with Complex Karyotype and Disease Progression

Publication date: Available online 24 August 2017
Source:Human Pathology
Author(s): Matthew W Rosenbaum, Olga Pozdnyakova, Julia T Geyer, Paola Dal Cin, Robert Hasserjian
Ring chromosome (RC) is a poorly understood genetic anomaly seen in myeloid neoplasms. This study aims to shed light on the clinical significance of this finding. We identified 96 cases of myeloid neoplasms with RC from 3 academic hospitals. Clinicopathologic features and overall- (OS) and leukemia-free survival were reviewed and compared to cases of myeloid neoplasms lacking RC. We identified 59 acute myeloid leukemias (AML-RC) and 37 myelodysplastic syndromes (MDS-RC) with RC identified on routine karyotyping. 75% of AML-RC and 97% of MDS-RC had complex (>3 independent cytogenetic abnormalities) karyotypes. The median OS of AML-RC with complex karyotype was significantly shorter than AML-RC patients with a non-complex (≤3 independent cytogenetic abnormalities) karyotype (P=.001), but similar to AML patients with complex karyotype lacking RC (p=n.s.). Compared to complex karyotype MDS lacking RC, MDS-RC patients had shorter leukemia-free survival (P=.016) and a trend for shorter overall survival (P=.10). RCs are associated with an inferior leukemia-free survival in MDS with complex karyotype. AML-RC with complex karyotype had similar outcomes to complex karyotype AML lacking RC, but shorter survival than AML-RC with a non-complex karyotype. RCs were sometimes lost after therapy or appeared during disease relapse, suggesting that they may be associated with genetic instability.



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Avoiding Surgical Skill Decay: A Systematic Review on the Spacing of Training Sessions

Publication date: Available online 24 August 2017
Source:Journal of Surgical Education
Author(s): Dario Cecilio-Fernandes, Fokie Cnossen, Debbie A.D.C. Jaarsma, René A. Tio
ObjectiveSpreading training sessions over time instead of training in just 1 session leads to an improvement of long-term retention for factual knowledge. However, it is not clear whether this would also apply to surgical skills. Thus, we performed a systematic review to find out whether spacing training sessions would also improve long-term retention of surgical skills.DesignWe searched the Medline, PsycINFO, Embase, Eric, and Web of Science online databases. We only included articles that were randomized trials with a sample of medical trainees acquiring surgical motor skills in which the spacing effect was reported. The quality and bias of the articles were assessed using the Cochrane Collaboration's risk of bias assessment tool.ResultsWith respect to the spacing effect, 1955 articles were retrieved. After removing duplicates and articles that did not meet the inclusion criteria, 11 articles remained. The overall quality of the experiments was "moderate." Trainees in the spaced condition scored higher in a retention test than students in the massed condition.ConclusionsOur systematic review showed evidence that spacing training sessions improves long-term surgical skills retention when compared to massed practice. However, the optimal gap between the re-study sessions is unclear.



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TEAM: A Low-Cost Alternative to ATLS for Providing Trauma Care Teaching in Haiti

Publication date: Available online 24 August 2017
Source:Journal of Surgical Education
Author(s): Anton Kurdin, Andrew Caines, Darrell Boone, Andrew Furey
ObjectiveTrauma resuscitation protocols have unified the care of trauma patients and significantly improved outcomes. However, the success of the Advanced Trauma Life Support course is difficult to reproduce in developing countries due to set-up costs, limitations of resources, and variations of practice. The objective of this study is to assess the Trauma Evaluation and Management (TEAM) course as a low-cost alternative for trauma resuscitation teaching in Low and Middle Income Countries (LMIC).DesignAs part of the Team Broken Earth initiative, TEAM course was provided to the health care professionals in Haiti. At its conclusion, participants were asked to complete a survey evaluating the course. Qualitative and quantitative data were analyzed to evaluate the perception of the course.SettingThe course was provided in Port-au-Prince, Haiti.ParticipantsA total of 80 health care professionals participated in the course. Response was obtained from 69 participants, which comprised of 32 physicians, 10 Emergency Medical Technicians (EMT), 22 nurses, and 5 medical trainees.ResultsThe course was well received by physicians, nurses, and EMT with an average score of 90.6%. Question analysis revealed a lower satisfaction of physicians for the course manual and teaching materials, and information related to decisions for transfer of patients. EMT consistently felt that the course was not tailored to their learning and practice needs. Written feedback demonstrated several areas of weaknesses including need for improvements in translations, hands-on practice, and educational materials.ConclusionsOverall, the TEAM course was well received. Analysis demonstrated a need for adjustments specific to LMIC including a focus on prehospital assessment, increased nursing responsibilities, and unavailability of specialist's referrals. Team Broken Earth intends to take these findings into consideration and continue to provide the TEAM course to other LMIC.



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Coronary Artery Calcium Imaging in the ROBINSCA Trial

Publication date: Available online 23 August 2017
Source:Academic Radiology
Author(s): Marleen Vonder, Carlijn M. van der Aalst, Rozemarijn Vliegenthart, Peter M.A. van Ooijen, Dirkjan Kuijpers, Jan Willem Gratama, Harry J. de Koning, Matthijs Oudkerk
Rationale and ObjectivesTo describe the rationale, design, and technical background of coronary artery calcium (CAC) imaging in the large-scale population-based cardiovascular disease screening trial (Risk Or Benefit IN Screening for CArdiovascular Diseases [ROBINSCA]).Materials and MethodsFirst, literature search was performed to review the logistics, setup, and settings of previously performed CAC imaging studies, and current clinical CAC imaging protocols of participating centers in the ROBINSCA trial were evaluated. A second literature search was performed to evaluate the impact of computed tomography parameter settings on CAC score.ResultsBased on literature reviews and experts opinion an imaging protocol accompanied by data management protocol was created for ROBINSCA. The imaging protocol should consist of a fixed tube voltage, individually tailored tube current setting, mid-diastolic electrocardiography-triggering, fixed field-of-view, fixed reconstruction kernel, fixed slice thickness, overlapping reconstruction and without iterative reconstruction. The analysis of scans is performed with one type and version of CAC scoring software, by two dedicated and experienced researchers. The data management protocol describes the organization of data handling between the coordinating center, participating centers, and core analysis center.ConclusionIn this paper we describe the rationale and technical considerations to be taken in developing CAC imaging protocol, and we present a detailed protocol that can be implemented for CAC screening purposes.



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T2 Star-weighted Angiography (SWAN) Allows to Concomitantly Assess the Prostate Contour While Detecting Fiducials Before MR-based Intensity-modulated Radiation Therapy in Prostate Carcinoma

Publication date: Available online 23 August 2017
Source:Academic Radiology
Author(s): Pierre-Antoine Dirajlal, Eva Jambon, Agnes Albat-Esquirou, Chloe Galmiche, Jean-Christophe Bernhard, Nicolas Grenier, Thibaud Haaser, François H. Cornelis
PurposeTo evaluate the performance of T2 star-weighted angiography (SWAN) to concomitantly assess the prostate contour while detecting fiducials before magnetic resonance (MR)-based intensity-modulated radiation therapy (IMRT) in prostate carcinoma.Materials and MethodsForty patients (mean age: 73.1 ± 7.5 years; average Gleason score: 7 ± 1; average prostate-specific antigen: 14.7 ± 11.6 ng/mL) underwent MR and computed tomography imaging before fiducial-based IMRT. MR protocol included SWAN, T2-weighted (T2w) and diffusion-weighted imaging in a first group (n = 20) and SWAN, T2w and T2-star weighted imaging in a second group (n = 20). In group 1, the depiction of fiducials, image sharpness and visibility of prostate boundaries were independently evaluated by 2 readers on SWAN, T2w or diffusion-weighted images. In group 2, a similar evaluation was performed by 2 other readers on SWAN and T2-star images only. Depiction of fiducials was compared to computed tomography findings.ResultsThe median scores of visibility of prostate boundaries, image sharpness and depiction of fiducials by SWAN were above average to excellent for all readers. In group 1, readers correctly located 56 of 57 (98.2%) and 47 of 57 (82.5%) fiducials, respectively; and 50 of 51 (98%), and 48 of 51 (88.2%) fiducials in group 2, respectively.ConclusionBy allowing adequate visualization of the prostate boundaries and high depiction of fiducial markers concomitantly, SWAN might be used for treatment planning of IMRT. The use of this sequence might simplify the registration process and limit any errors associated with image fusion.



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Lepidic Predominant Pulmonary Lesions (LPL)

Publication date: Available online 24 August 2017
Source:Academic Radiology
Author(s): Jeffrey B. Alpert, Henry Rusinek, Jane P. Ko, Bari Dane, Harvey I. Pass, Bernard K. Crawford, Amy Rapkiewicz, David P. Naidich
Rationale and ObjectivesThis study aimed to differentiate pathologically defined lepidic predominant lesions (LPL) from more invasive adenocarcinomas (INV) using three-dimensional (3D) volumetric density and first-order texture histogram analysis of surgically excised stage 1 lung adenocarcinomas.Materials and MethodsThis retrospective study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. Sixty-four cases of pathologically proven stage 1 lung adenocarcinoma surgically resected between September 2006 and October 2015, including LPL (n = 43) and INV (n = 21), were evaluated using high-resolution computed tomography. Quantitative measurements included nodule volume, percent solid volume (% solid), and first-order texture histogram analysis including skewness, kurtosis, entropy, and mean nodule attenuation within each histogram quartile. Binomial logistic regression models were used to identify the best set of parameters distinguishing LPL from INV.ResultsUnivariate analysis of 3D volumetric density and histogram features was statistically significant between LPL and INV groups (P < .05). Accuracy of a binomial logistic model to discriminate LPL from INV based on size and % solid was 85.9%. With optimized probability cutoff, the model achieves 81% sensitivity, 76.7% specificity, and area under the receiver operating characteristic curve of 0.897 (95% confidence interval, 0.821–0.973). An additional model based on size and mean nodule attenuation of the third quartile (Hu_Q3) of the histogram achieved similar accuracy of 81.3% and area under the receiver operating characteristic curve of 0.877 (95% confidence interval, 0.790–0.964).ConclusionsBoth 3D volumetric density and first-order texture analysis of stage 1 lung adenocarcinoma allow differentiation of LPL from more invasive adenocarcinoma with overall accuracy of 85.9%–81.3%, based on multivariate analyses of either size and % solid or size and Hu_Q3, respectively.



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Promoting Collaborations Between Radiologists and Scientists

Publication date: Available online 24 August 2017
Source:Academic Radiology
Author(s): John-Paul J. Yu, Bradley M. Spieler, Tiffany L. Chan, Elizabeth M. Johnson, Vikas Gulani, Kim L. Sandler, Ponnada A. Narayana, Winnie A. Mar, James M. Brian, Chin K. Ng
Radiology as a discipline thrives on the dynamic interplay between technological and clinical advances. Progress in almost all facets of the imaging sciences is highly dependent on complex tools sourced from physics, engineering, biology, and the clinical sciences to obtain, process, and view imaging studies. The application of these tools, however, requires broad and deep medical knowledge about disease pathophysiology and its relationship with medical imaging. This relationship between clinical medicine and imaging technology, nurtured and fostered over the past 75 years, has cultivated extraordinarily rich collaborative opportunities between basic scientists, engineers, and physicians. In this review, we attempt to provide a framework to identify both currently successful collaborative ventures and future opportunities for scientific partnership. This invited review is a product of a special working group within the Association of University Radiologists-Radiology Research Alliance.



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The Sixth Stage

Publication date: Available online 24 August 2017
Source:Academic Radiology
Author(s): Mohsin Mukhtar, Richard B. Gunderman




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Thoracic Quantitative Computed Tomography (QCT) Can Sensitively Monitor Bone Mineral Metabolism

Publication date: Available online 23 August 2017
Source:Academic Radiology
Author(s): Song Shou Mao, Dong Li, Younus Saleem Syed, Yanlin Gao, Yanting Luo, Ferdinand Flores, Janis Child, MacKenzie Cervantes, Kamyar Kalantar-Zadeh, Matthew J. Budoff
Rationale and ObjectiveSensitive detection of bone mineral density (BMD) change is a key issue to monitor and evaluate the individual bone health status, as well as bone metabolism and bone mineral status. The ability to use thoracic quantitative computed tomography (QCT) to detect the annual change of BMD remains unclear. We aimed to investigate the sensitivity in detecting age-related bone mineral loss using the thoracic QCT from the electrocardiographically gated heart scans in comparison to whole-body dual-energy X-ray absorptiometry (DXA) and standard lumbar QCT.Materials and MethodsA total of 121 asymptomatic patients' imaging data, including DXA whole body scan, cardiac CT scan, and abdomen scans were analyzed. The BMD of the thoracolumbar spine, upper, and lower extremities were measured using QCT and DXA, respectively. The age-related annual rate of bone density loss was computed and compared to the thoracic and lumbar QCT, as well DXA measures.ResultsThe age-related annual rate of bone loss with QCT was −0.70 mg/mL³ (−0.75%/y) in women, −0.83 mg/mL³ (−0.86%/y) in men in the thoracic and the lumbar trabecular QCT, respectively. Compared to the QCT, DXA demonstrates a lower annual rate of bone loss in the area of BMD measurement (P < .05 in all, excluding legs of women) in −0.45, −0.42, −0.67, and −0.46 in women, in −0.32, −0.02, −0.12, and −0.08 in men for thoracic, lumbar, leg, and arm, respectively.ConclusionWe conclude that the thoracic and the lumbar QCT provide a similar and more sensitive method for detecting bone mineral loss when compared to DXA.



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The Cerebellum is a Common Site of Affection in Leigh Syndrome

Publication date: Available online 24 August 2017
Source:Pediatric Neurology
Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub




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Severe Neutropenia and Anemia in a Child with Epilepsy and Copper Deficiency on a Ketogenic Diet

Publication date: Available online 24 August 2017
Source:Pediatric Neurology
Author(s): Houman Rashidian, YM Christiana Liu, Michael T Geraghty, Jeff Kobayashi, Elizabeth J. Donner, Robert J. Klaassen




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Alice in Wonderland Syndrome: a Historical and Medical Review

Publication date: Available online 24 August 2017
Source:Pediatric Neurology
Author(s): Osman Farooq, Edward J. Fine
Alice in Wonderland syndrome is a disorienting neurological condition that affects human perception to the senses of vision, hearing, touch, sensation and the phenomenon of time. Individuals affected with Alice in Wonderland syndrome can experience alterations in their perception to the size of objects or their own body parts, known as metamorphopsias. It is known to occur in conditions including migraine, epilepsy, as well as certain intoxicants and infectious diseases. The name refers to Lewis Carrol's well-known children's book Alice's Adventures in Wonderland, in which the title character experiences alterations of sensation in which she felt that her body had grown too tall or too small, or parts of her body were changing shape, size or relationship to the rest of her body. The syndrome was described in 1952 by Caro Lippman, and given its name in 1955 by John Todd. The metamorphopsias characteristic of this condition are also sometimes referred to as Lilliputian hallucinations, as a reference to the fictional island of Lilliput in the novel Gulliver's Travels, written by Jonathan Swift in 1726. As such, many literary and medical publications have roots in the description of this syndrome. The purpose of this review is to summarize the literary and historical significance of Alice in Wonderland syndrome as well as to provide the reader with a medical overview of the condition.



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Acylpeptide Hydrolase is a Component of the Cellular Response to DNA Damage

Publication date: Available online 24 August 2017
Source:DNA Repair
Author(s): Zhihong Zeng, Stuart L. Rulten, Claire Breslin, Anastasia Zlatanou, Victoria Coulthard, Keith W. Caldecott
Acylpeptide hydrolase (APEH) deacetylates N-alpha-acetylated peptides and selectively degrades oxidised proteins, but the biochemical pathways that are regulated by this protease are unknown. Here, we identify APEH as a component of the cellular response to DNA damage. Although APEH is primarily localised in the cytoplasm, we show that a sub-fraction of this enzyme is sequestered at sites of nuclear damage following UVA irradiation or following oxidative stress. We show that localization of APEH at sites of nuclear damage is mediated by direct interaction with XRCC1, a scaffold protein that accelerates the repair of DNA single-strand breaks. We show that APEH interacts with the amino-terminal domain of XRCC1, and that APEH facilitates both single-strand break repair and cell survival following exposure to H2O2 in human cells. These data identify APEH as a novel proteolytic component of the DNA damage response.



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Proximity effects in chromosome aberration induction by low-LET ionizing radiation

Publication date: Available online 24 August 2017
Source:DNA Repair
Author(s): John James Tello Cajiao, Mario Pietro Carante, Mario Antonio Bernal Rodriguez, Francesca Ballarini
Although chromosome aberrations are known to derive from distance-dependent mis-rejoining of chromosome fragments, evaluating whether a certain model describes such "proximity effects" better than another one is complicated by the fact that different approaches have often been tested under different conditions. Herein, a biophysical model ("BIANCA", i.e. BIophysical ANalysis of Cell death and chromosome Aberrations) was upgraded, implementing explicit chromosome-arm domains and two new models for the dependence of the rejoining probability on the fragment initial distance, r. Such probability was described either by an exponential function like exp(-r/r0), or by a Gaussian function like exp(-r²/2σ²), where r0 and σ were adjustable parameters. The second, and last, parameter was the yield of "Cluster Lesions" (CL), where "Cluster Lesion" defines a critical DNA damage producing two independent chromosome fragments. The model was applied to low-LET-irradiated lymphocytes (doses: 1–4Gy) and fibroblasts (1-6.1Gy). Good agreement with experimental yields of dicentrics and centric rings, and thus their ratio ("F-ratio"), was found by both the exponential model (with r0=0.8μm for lymphocytes and 0.7μm for fibroblasts) and the Gaussian model (with σ=1.1μm for lymphocytes and 1.3μm for fibroblasts). While the former also allowed reproducing dose-responses for excess acentric fragments, the latter substantially underestimated the experimental curves. Both models provided G-ratios (ratio of acentric to centric rings) higher than those expected from randomness, although the values calculated by the Gaussian model were lower than those calculated by the exponential one. For lymphocytes the calculated G-ratios were in good agreement with the experimental ones, whereas for fibroblasts both models substantially underestimated the experimental results, which deserves further investigation. This work suggested that, although both models performed better than a step model (which previously allowed reproducing the F-ratio but underestimated the G-ratio), an exponential function describes proximity effects better than a Gaussian one.



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