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1.
ANZ J Surg ; 92(11): 2961-2967, 2022 11.
Article in English | MEDLINE | ID: mdl-35841184

ABSTRACT

BACKGROUND: Neoadjuvant long course chemoradiotherapy (NLCRT) for rectal cancer can result in complete pathological response (pCR). In 2017, we started offering patients who had a complete clinical response (cCR), a choice between total mesorectal excision (TME) and an intensive surveillance or 'watch and wait' (W&W) program. We report the early outcomes of this prospective study. METHODS: All patients undergoing NLCRT from 2017 to 2019 were included. All patients were restaged at 8 weeks, and those who had a cCR were offered TME or W&W. RESULTS: Of 59 patients who underwent NLCRT, 55 had restaging. Eleven of these patients had a cCR (20%). Three chose to have TME and all had a pCR. Eight were enrolled in W&W. Two patients were diagnosed with local regrowth and underwent TME at 7 and 17 months after NLCRT. A further nine patients, who were surgically unfit or refused TME, and had an excellent response to NLCRT, but one that did not reach criteria for a cCR, were also managed with W&W. Of these, two patients developed regrowth with distant metastases. From 2017 to 2019, of the 17 patients who were managed with a W&W approach, 13 patients have remained regrowth free after a median of 28 (13-58) months of W&W. CONCLUSION: Preliminary findings suggest management with W&W, following cCR, may be a safe alternative to TME. There have so far been no instances of distant failure, and those with cCR that had regrowth, were identified early and successfully managed with salvage TME.


Subject(s)
Rectal Neoplasms , Watchful Waiting , Humans , Prospective Studies , Watchful Waiting/methods , Neoplasm Recurrence, Local/diagnosis , Treatment Outcome , Rectal Neoplasms/pathology , Chemoradiotherapy/methods , Neoadjuvant Therapy
2.
Mol Ecol ; 31(1): 238-251, 2022 01.
Article in English | MEDLINE | ID: mdl-34614231

ABSTRACT

Insights into the generation of diversity in both plants and animals have relied heavily on studying speciation in adaptive radiations. Russia's Lake Baikal has facilitated a putative adaptive radiation of cottid fishes (sculpins), some of which are highly specialized to inhabit novel niches created by the lake's unique geology and ecology. Here, we test evolutionary relationships and novel morphological adaptation in a piece of this radiation: the Baikal cottid genus, Cottocomephorus, a morphologically derived benthopelagic genus of three described species. We used a combination of mitochondrial DNA and restriction site associated DNA sequencing from all Cottocomephorus species. Analysis of mitochondrial cytochrome b haplotypes was only able to two resolve two lineages: C. grewingkii and C. comephoroides/inermis. Phylogenetic inference, principal component analysis, and faststructure of genome-wide SNPs uncovered three lineages within Cottocomephorus: C. comephoroides, C. inermis and C. grewingkii. We found recent divergence and admixture between C. comephoroides and C. inermis and deep divergence between these two species and C. grewingkii. Contrasting other fish radiations, we found no evidence of ancient hybridization among Cottocomephorus species. Digital morphology revealed highly derived pelagic phenotypes that reflect divergence by specialization to the benthopelagic niche in Cottocomephorus. Among Cottocomephorus species, we found evidence of ongoing adaptation to the pelagic zone. This pattern highlights the importance of speciation along a benthic-pelagic gradient seen in Cottocomephorus and across other adaptive fish radiations.


Subject(s)
Fishes , Lakes , Animals , DNA, Mitochondrial/genetics , Fishes/genetics , Genetic Speciation , Hybridization, Genetic , Phylogeny
3.
Acta Parasitol ; 64(3): 603-611, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31286355

ABSTRACT

BACKGROUND: The gills of Red River Pupfish (Cyprinodon rubrofluviatilis) collected from Kansas and Texas, U.S.A., were found to be infected with three monogenoideans, Fundulotrema prolongis, Gyrodactylus rubrofluviatilae n. sp., and a species of Salsuginus. RESULTS: Gyrodactylus rubrofluviatilae n. sp. appears to be a member of a group of six closely related species possessing hamuli with mesially folded roots and a linguiform ventral bar shield, and parasitizing closely related species of Cyprinodon of the North American Gulf Coast and inland waters of the Southwestern United States and northern México. Gyrodactylus rubrofluviatilae n. sp. differs from its close congeners in the morphology of the hamuli, ventral bar, ventral bar shield, and marginal hooks. Because the morphology of the male copulatory complex was not determined of what we believe will eventually be a new species of Salsuginus, a species description is deferred. This is the first report of any parasite from this host. CONCLUSIONS: Many North American species currently recognized within the Cyprinodontiformes have not yet been surveyed for species of Fundulotrema, Gyrodactylus, or Salsuginus. This, coupled with the high host specificity generally recognized for these monogeneans, portends there are likely additional new species yet to be discovered. When possible, to help augment morphological data, further studies should employ comprehensive intra- and interspecies molecular analyses to help resolve host-parasite phylogenies.


Subject(s)
Fish Diseases/parasitology , Killifishes/parasitology , Trematoda/isolation & purification , Trematode Infections/veterinary , Animals , Female , Gills/parasitology , Kansas , Male , Phylogeny , Texas , Trematoda/classification , Trematoda/genetics , Trematode Infections/parasitology
4.
Proc Natl Acad Sci U S A ; 116(10): 3994-3999, 2019 Mar 05.
Article in English | MEDLINE | ID: mdl-30760584

ABSTRACT

Ultrahigh-power terahertz (THz) radiation sources are essential for many applications, for example, THz-wave-based compact accelerators and THz control over matter. However, to date none of the THz sources reported, whether based upon large-scale accelerators or high-power lasers, have produced THz pulses with energies above the millijoule (mJ) level. Here, we report a substantial increase in THz pulse energy, as high as tens of mJ, generated by a high-intensity, picosecond laser pulse irradiating a metal foil. A further up-scaling of THz energy by a factor of ∼4 is observed when introducing preplasmas at the target-rear side. Experimental measurements and theoretical models identify the dominant THz generation mechanism to be coherent transition radiation, induced by the laser-accelerated energetic electron bunch escaping the target. Observation of THz-field-induced carrier multiplication in high-resistivity silicon is presented as a proof-of-concept application demonstration. Such an extremely high THz energy not only triggers various nonlinear dynamics in matter, but also opens up the research era of relativistic THz optics.

5.
J Fish Biol ; 93(5): 778-791, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30101564

ABSTRACT

The extent and nature of genetic differentiation in Semotilus atromaculatus, one of the most abundant and widespread leuciscids in North America, were evaluated based on mitochondrial (mt) and nuclear DNA sequence variation. Phylogenetic relationships were first inferred based on a fragment of the cytochrome b (cytb) region and the nuclear intron s7 gene for S. atromaculatus and all other congeners as well as representative species from all other genera in the creek chub-plagopterin clade. The phylogeography of major haplogroups of S. atromaculatus was also assessed according to variation in a fragment of the mitochondrial cytb region from 567 individuals across its range. All analyses identified S. thoreauianus, S. lumbee and S. corporalis as reciprocally monophyletic groups. Analyses of nuclear sequence variation resolved S. atromaculatus as a single clade, where S. thoreauianus and S. lumbee were recovered as the sister group to S. atromaculatus, and S. corporalis was resolved as sister to all other species in the genus. Analyses of mtDNA sequence variation recovered S. atromaculatus as three well supported and differentiated monophyletic groups, with a widespread genetically homogeneous lineage extending across most of the current range of the species; a more geographically restricted and geographically structured lineage in the southern Appalachians, sister group to S. lumbee; and a geographically restricted lineage was identified from two Gulf Slope basins. Evidence of complex mito-nuclear discordance and phylogeographic differentiation within S. atromaculatus illustrates that further analysis of widespread species is warranted to understand North American freshwater fish diversity and distributions.


Subject(s)
Cyprinidae/classification , Cyprinidae/genetics , Genetic Variation , Phylogeny , Animals , Cell Nucleus/genetics , DNA, Mitochondrial/genetics , Fish Proteins/genetics , Fresh Water , Introns/genetics , North America , Phylogeography , Sequence Analysis, DNA , Species Specificity
6.
Rev Sci Instrum ; 88(9): 093512, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28964232

ABSTRACT

A technique for the creation of free-standing cryogenic targets for laser-driven ion acceleration is presented, which allows us to create solid state targets consisting of initially gaseous materials. In particular, the use of deuterium and the methods for its preparation as a target material for laser-driven ion acceleration are discussed. Moving in the phase diagram through the liquid phase leads to the substance covering an aperture on a cooled copper frame where it is solidified through further cooling. An account of characterization techniques for target thickness is given, with a focus on deducing thickness values from distance values delivered by chromatic confocal sensors.

7.
Retina ; 37(7): 1329-1336, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28633153

ABSTRACT

PURPOSE: To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). METHODS: Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). RESULTS: The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. CONCLUSION: In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.


Subject(s)
Dark Adaptation , Macula Lutea/pathology , Retinal Drusen/etiology , Tomography, Optical Coherence/methods , Visual Acuity , Wet Macular Degeneration/complications , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Retinal Drusen/diagnosis , Retinal Drusen/physiopathology , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/physiopathology
8.
JAMA Ophthalmol ; 135(6): 570-575, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28448669

ABSTRACT

Importance: Age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment in older adults in the United States, yet little is known about whether AMD is appropriately diagnosed in primary eye care. Objectives: To examine the prevalence of eyes with AMD in patients seen in primary eye care clinics who purportedly have normal macular health per their medical record and the association of AMD with patient and physician characteristics. Design, Setting, and Participants: In this cross-sectional study of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or older with normal macular health per medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist were enrolled from May 1, 2009, through December 31, 2011. Data analysis was performed from May 1, 2016, through December 20, 2016. Main Outcomes and Measures: Presence of AMD as defined by the Clinical Age-Related Maculopathy Staging system based on color fundus photography and a masked grader. Types of AMD-associated lesions were noted. Patient health and physician characteristics were collected. Results: The sample consisted of 1288 eyes from 644 participants (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611 white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320 (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of undiagnosed AMD was not different for ophthalmologists and optometrists (age adjusted OR, 0.99; 95% CI, 0.71-1.36; P = .94). Conclusions and Relevance: Approximately 25.0% of eyes deemed to be normal based on dilated eye examination by primary eye care physicians had macular characteristics that indicated AMD revealed by fundus photography and trained raters. A total of 30.0% of eyes with undiagnosed AMD had AMD with large drusen that would have been treatable with nutritional supplements had it been diagnosed. Improved AMD detection strategies may be needed in primary eye care as more effective treatment strategies for early AMD become available in the coming years.


Subject(s)
Diagnostic Errors/statistics & numerical data , Diagnostic Techniques, Ophthalmological , Macular Degeneration/epidemiology , Primary Health Care/statistics & numerical data , Aged , Alabama/epidemiology , Cross-Sectional Studies , Female , Humans , Macular Degeneration/diagnosis , Male , Middle Aged , Odds Ratio , Prevalence , Prospective Studies , Tomography, Optical Coherence
10.
Nat Commun ; 7: 12891, 2016 09 14.
Article in English | MEDLINE | ID: mdl-27624920

ABSTRACT

Control of the collective response of plasma particles to intense laser light is intrinsic to relativistic optics, the development of compact laser-driven particle and radiation sources, as well as investigations of some laboratory astrophysics phenomena. We recently demonstrated that a relativistic plasma aperture produced in an ultra-thin foil at the focus of intense laser radiation can induce diffraction, enabling polarization-based control of the collective motion of plasma electrons. Here we show that under these conditions the electron dynamics are mapped into the beam of protons accelerated via strong charge-separation-induced electrostatic fields. It is demonstrated experimentally and numerically via 3D particle-in-cell simulations that the degree of ellipticity of the laser polarization strongly influences the spatial-intensity distribution of the beam of multi-MeV protons. The influence on both sheath-accelerated and radiation pressure-accelerated protons is investigated. This approach opens up a potential new route to control laser-driven ion sources.

11.
J Hazard Mater ; 318: 694-701, 2016 Nov 15.
Article in English | MEDLINE | ID: mdl-27484945

ABSTRACT

A small scale sample nuclear waste package, consisting of a 28mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500keV), with a source size of <0.5mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30cm(2) scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.

12.
Invest Ophthalmol Vis Sci ; 57(2): 739-45, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26906160

ABSTRACT

PURPOSE: Subretinal drusenoid deposits (SDD) have been associated with the progression to late age-related macular degeneration (AMD). To determine whether SDD in eyes in normal macular health increases risk for early AMD, this study examined the association between presence of SDD at baseline in a cohort of older adults in normal macular health and incident AMD 3 years later. METHODS: Subjects enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) were assessed for the presence of SDD using color fundus photos, infrared reflectance and fundus autofluorescence images, and spectral-domain optical coherence tomography volumes. The study sample included 799 eyes from 455 participants in normal macular health per grading of color fundus photographs using the 9-step Age-Related Eye Disease Study (AREDS) classification system. Age-related macular degeneration was defined as eyes having an AREDS grade ≥2 at the 3-year follow-up. RESULTS: Twenty-five percent of participants had SDD in one or both eyes at baseline. At follow-up visit, 11.9% of eyes in the sample developed AMD. Compared to eyes without SDD, those with SDD were 2.24 (95% confidence interval [CI] 1.36-3.70) times more likely to have AMD at follow-up. After adjusting for age, C-reactive protein quartile, and family history of AMD, the association persisted. CONCLUSIONS: Results suggest that SDD in older eyes with normal macular health as defined by the AREDS scale is a risk factor for the development of early AMD. Older adults in seemingly normal macular health yet having SDD may warrant closer clinical monitoring for the possible onset of early AMD.


Subject(s)
Macular Degeneration/epidemiology , Retinal Drusen/epidemiology , Aged , Aged, 80 and over , Alabama/epidemiology , Cohort Studies , Diagnostic Techniques, Ophthalmological , Disease Progression , Female , Fluorescein Angiography/methods , Follow-Up Studies , Humans , Macular Degeneration/pathology , Male , Middle Aged , Optical Imaging/methods , Prospective Studies , Retinal Drusen/pathology , Risk Factors , Tomography, Optical Coherence
13.
Ophthalmology ; 123(5): 1090-100, 2016 05.
Article in English | MEDLINE | ID: mdl-26875000

ABSTRACT

PURPOSE: To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. METHODS: Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. MAIN OUTCOME MEASURES: Prevalence of SDD in participants with and without AMD. RESULTS: Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. CONCLUSIONS: Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance.


Subject(s)
Macula Lutea/diagnostic imaging , Multimodal Imaging , Optic Disk/diagnostic imaging , Retinal Drusen/epidemiology , Wet Macular Degeneration/epidemiology , Aged , Aged, 80 and over , Apolipoprotein A-I/blood , Apolipoproteins B/blood , C-Reactive Protein/metabolism , Complement System Proteins/metabolism , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Retinal Drusen/blood , Retinal Drusen/diagnostic imaging , Tomography, Optical Coherence , Wet Macular Degeneration/blood , Wet Macular Degeneration/diagnostic imaging
14.
Neuropharmacology ; 99: 369-78, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26116816

ABSTRACT

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and other disorders. However, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed SSRIs for non-mood disorders. Here we evaluated SSRI effects on neural volumetrics in depressed and nondepressed monkeys. METHODS: 42 socially-housed cynomolgus monkeys were randomized to treatment balanced on pretreatment depressive behavior and body weight. Monkeys were trained for oral administration of placebo or 20 mg/kg sertraline HCl daily for 18 months and depressive and anxious behavior recorded. Volumes of neural regions of interest in depression were measured in magnetic resonance images and analyzed by 2 (depressed, nondepressed)×2 (placebo, sertraline) ANOVA. RESULTS: Sertraline reduced anxiety (p=0.04) but not depressive behavior (p=0.43). Left Brodmann's Area (BA) 32 was smaller in depressed than nondepressed monkeys (main effect of depression: p<0.05). Sertraline and depression status interacted to affect volumes of left Anterior Cingulate Cortex (ACC), left BA24, right hippocampus (HC), and right anterior HC (sertraline×depression interactions: all p's<0.05). In the Placebo group, depressed monkeys had smaller right anterior HC and left ACC than nondepressed monkeys. In nondepressed monkeys, sertraline reduced right HC volume, especially right anterior HC volume. In depressed monkeys sertraline increased left ACC volume. In nondepressed monkeys, sertraline reduced left BA24 volumes resulting in smaller BA24 volumes in nondepressed than sertraline-treated depressed monkeys. CONCLUSIONS: These observations suggest that SSRIs may differentially affect neural structures in depressed and nondepressed individuals.


Subject(s)
Antidepressive Agents/pharmacology , Brain/drug effects , Depressive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/pharmacology , Sertraline/pharmacology , Administration, Oral , Animals , Antidepressive Agents/blood , Anxiety/drug therapy , Anxiety/pathology , Anxiety/physiopathology , Behavior, Animal/drug effects , Brain/pathology , Depressive Disorder/pathology , Depressive Disorder/physiopathology , Female , Hydroxyindoleacetic Acid/cerebrospinal fluid , Macaca fascicularis , Magnetic Resonance Imaging , Organ Size , Random Allocation , Selective Serotonin Reuptake Inhibitors/blood , Sertraline/analogs & derivatives , Sertraline/blood , Treatment Outcome
15.
Appl Opt ; 53(31): I41-4, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-25402936

ABSTRACT

Significant advances have been made over the last decade to improve the performance, efficiency, and contrast of high peak and average power laser systems, driven by their use in a wide variety of fields, from the industrial to the scientific. As the contrast of the lasers has improved, interactions with contrasts of 1012 are now routinely undertaken. At such high contrasts, there is negligible preplasma formation and the ionized surface layer created by subpicosecond-duration pulses typically forms a highly reflective "plasma mirror" capable of reflecting between 70% and 90% of the incident energy. Although such interactions are of significant interest for applications such as harmonic source production and to enable the underlying physics to be studied, their low absorption can limit their usefulness for applications such as space debris removal.

16.
Dev Biol ; 392(2): 209-20, 2014 Aug 15.
Article in English | MEDLINE | ID: mdl-24907417

ABSTRACT

Sonic hedgehog (SHH) plays a central role in patterning numerous embryonic tissues including, classically, the developing limb bud where it controls digit number and identity. This study utilises the polydactylous Silkie (Slk) chicken breed, which carries a mutation in the long range limb-specific regulatory element of SHH, the ZRS. Using allele specific SHH expression analysis combined with quantitative protein analysis, we measure allele specific changes in SHH mRNA and concentration of SHH protein over time. This confirms that the Slk ZRS enhancer mutation causes increased SHH expression in the posterior leg mesenchyme. Secondary consequences of this increased SHH signalling include increased FGF pathway signalling and growth as predicted by the SHH/GREM1/FGF feedback loop and the Growth/Morphogen models. Manipulation of Hedgehog, FGF signalling and growth demonstrate that anterior-ectopic expression of SHH and induction of preaxial polydactyly is induced secondary to increased SHH signalling and Hedgehog-dependent growth directed from the posterior limb. We predict that increased long range SHH signalling acts in combination with changes in activation of SHH transcription from the Slk ZRS allele. Through analysis of the temporal dynamics of anterior SHH induction we predict a gene regulatory network which may contribute to activation of anterior SHH expression from the Slk ZRS.


Subject(s)
Enhancer Elements, Genetic/genetics , Gene Expression Regulation, Developmental/physiology , Hedgehog Proteins/genetics , Mutation/genetics , Polydactyly/genetics , Signal Transduction/physiology , Animals , Chick Embryo , Computational Biology , DNA Primers/genetics , Electrophoretic Mobility Shift Assay , Fibroblast Growth Factors/metabolism , Gene Expression Profiling , Gene Regulatory Networks/genetics , Hedgehog Proteins/physiology , In Situ Hybridization , Models, Biological , Polymorphism, Restriction Fragment Length , Real-Time Polymerase Chain Reaction
17.
Ann Surg ; 259(5): 852-60, 2014 May.
Article in English | MEDLINE | ID: mdl-24509201

ABSTRACT

OBJECTIVE: The aim of this review was to assess the safety and effectiveness of esophageal stents in the management of benign esophageal perforation and in the management of esophageal anastomotic leaks. BACKGROUND: Benign esophageal perforation and postoperative esophageal anastomotic leak are often encountered. Endoscopic placement of esophageal stent across the site of leakage might help control the sepsis and reduce the mortality and morbidity. METHODS: All the published case series reporting the use of metallic and plastic stents in the management of postoperative anastomotic leaks, spontaneous esophageal perforations, and iatrogenic esophageal perforations were identified from MEDLINE, EMBASE, and PubMed (1990-2012). Primary outcomes assessed were technical success rates and complete healing rates. Secondary outcomes assessed were stent migration rates, stent perforation rates, duration of hospital stay, time to stent removal, and mortality rates. A pooled analysis was performed and subgroup analysis was performed for plastic versus metallic stents and anastomotic leaks versus perforations separately. RESULTS: A total of 27 case series with 340 patients were included. Technical and clinical success rates of stenting were 91% and 81%, respectively. Stent migration rates were significantly higher with plastic stents than with metallic stents (40/148 vs 13/117 patients, respectively; P = 0.001). Patients with metallic stents had significantly higher incidence of postprocedure strictures (P = 0.006). However, patients with plastic stents needed significantly higher number of reinterventions (P = 0.005). Mean postprocedure hospital stay varied from 8 days to 51 days. There was no significant difference in the primary or secondary outcomes when stenting was performed for anastomotic leaks or perforations. CONCLUSIONS: Endoscopic management of esophageal anastomotic leaks and perforations with the use of esophageal stents is technically feasible. It seems to be safe and effective when performed along with mediastinal or pleural drainage. Esophageal stent can, therefore, be considered as a treatment option in the management of patients who present early after esophageal perforation or anastomotic leak with limited mediastinal or pleural contamination.


Subject(s)
Anastomotic Leak/surgery , Esophageal Perforation/surgery , Esophagus/surgery , Mediastinal Diseases/surgery , Outcome Assessment, Health Care , Stents/standards , Anastomosis, Surgical/adverse effects , Anastomotic Leak/epidemiology , Esophageal Perforation/mortality , Esophagoscopy/methods , Global Health , Humans , Incidence , Mediastinal Diseases/mortality , Prosthesis Design , Reoperation , Survival Rate/trends
18.
Postgrad Med J ; 89(1050): 197-201, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23412393

ABSTRACT

Adenocarcinoma of the small intestine is rare in comparison with other gastrointestinal malignancies but its incidence is rising. It often presents at an advanced stage due to the non-specific symptomatology. More recent advances in small intestinal visualisation including video capsule endoscopy and double balloon enteroscopy may facilitate diagnosis in patients with suspected small intestinal neoplasia. At present aggressive surgical resection provides the best chance of cure of small intestinal adenocarcinoma. Despite apparent curative resection the long-term outlook remains poor. The role of adjuvant chemotherapy is not well defined due to the rarity of the disease and lack of randomised controlled trials; however, there appears to be a survival benefit in advanced disease with the use of oxaliplatin and 5-fluorouracil. We reviewed the clinical aspects of this aggressive condition focusing on the pathological associations, available diagnostic modalities and current management options. Three cases are included to illustrate the review.


Subject(s)
Adenocarcinoma/diagnosis , Capsule Endoscopy , Double-Balloon Enteroscopy , Fluorouracil/therapeutic use , Intestinal Neoplasms/diagnosis , Intestine, Small/pathology , Organoplatinum Compounds/therapeutic use , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Aged , Celiac Disease/complications , Celiac Disease/pathology , Chemotherapy, Adjuvant , Cystic Fibrosis/complications , Cystic Fibrosis/pathology , Female , Humans , Intestinal Neoplasms/pathology , Intestinal Neoplasms/therapy , Male , Nausea , Oxaliplatin , Prognosis , Sensitivity and Specificity , Weight Loss
19.
Ulster Med J ; 82(3): 160-3, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24505151

ABSTRACT

OBJECTIVE: Colorectal cancer (CRC) is the third most common type of cancer with resulting major mortality. In a bid to reduce the mortality, bowel cancer screening has been established in the United Kingdom. The screening programme was commenced in Northern Ireland in 2010 within the Northern Health and Social Care Trust, following its implementation in England and Scotland. This study aimed to look at early outcome data for bowel cancer screening in Northern Ireland and compare data with other regions in the UK. DESIGN: A retrospective analysis was conducted of patients who tested faecal occult blood (FOB) positive and attended for pre-assessment between May 2010 and May 2011. Data was also collected from the computerised endoscopy database (Endoscribe®). Patient demographics, colonoscopic depth of insertion, findings and complications were documented. Subsequent surgical management, pathological staging and final outcome were also noted. RESULTS: 182 patients attended for pre-assessment in the time frame and 178 patients proceeded to colonoscopy. The commonest pathology encountered was polyps, identified in 95 (52.7%) patients. Macroscopically 13 cancers were seen on endoscopy and a further two were found on post-operative histology of polyps that were not amenable to endoscopic resection. In addition, 5 malignant polyps were found on histological analysis of the excised polyps. The staging of cancers was favourable with 35% being Dukes' A stage. CONCLUSION: Outcomes from the first year of colorectal cancer screening in the Northern Trust are in keeping with early results from previous studies in terms of cancer detection rates per colonoscopy and proportion of early stage cancers. However, the adenoma detection rate was higher than anticipated.


Subject(s)
Colonic Polyps/pathology , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Occult Blood , Colonic Polyps/surgery , Early Detection of Cancer , Female , Humans , Male , Mass Screening , Retrospective Studies
20.
Mol Phylogenet Evol ; 62(1): 427-46, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22056492

ABSTRACT

Accurate delimitation of species is a critical first step in protecting biodiversity. Detection of distinct species is especially important for groups of organisms that inhabit sensitive environments subject to recent degradation, such as creeks, springs, and rivers in arid or semi-desert regions. The genus Dionda currently includes six recognized and described species of minnows that live in clear springs and spring-fed creeks of Texas, New Mexico (USA), and northern Mexico, but the boundaries, delimitation, and characterization of species in this genus have not been examined rigorously. The habitats of some of the species in this genus are rapidly deteriorating, and many local populations of Dionda have been extirpated. Considering the increasing concerns over degradation of their habitat, and pending a more detailed morphological revision of the genus, we undertook a molecular survey based on four DNA regions to examine variation over the range of the genus, test species boundaries, and infer phylogenetic relationships within Dionda. Based on analyses of two mitochondrial (cytb and D-loop) and two nuclear (Rag1 and S7) DNA regions from specimens collected throughout the range of Dionda, we identified 12 distinct species in the genus. Formerly synonymized names are available for two of these species, and four other species remain undescribed. We also redefine the known range of six species. The limited distribution of several of the species, coupled with widespread habitat degradation, suggests that many of the species in this genus should be targets for conservation and recovery efforts.


Subject(s)
Cyprinidae/genetics , Genes, Mitochondrial , Genes, RAG-1 , Genetic Variation , Phylogeny , Animals , Bayes Theorem , Cyprinidae/classification , Likelihood Functions , Markov Chains , Mexico , Molecular Sequence Data , Sequence Analysis, DNA , United States
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