Punzi-loss:: a non-differentiable metric approximation for sensitivity optimisation in the search for new particles.

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example.

Food security is related to adult type 2 diabetes control over time in a United States safety net primary care clinic population.

BACKGROUND/OBJECTIVES: Successful Type 2 diabetes management requires adopting a high nutrient-density diet made up of food items that both meet dietary needs and preferences and can be feasibly obtained on a regular basis. However, access to affordable, nutrient-dense foods often is lacking in poorer neighbourhoods. Therefore, low food security should directly impair glucose control, even when patients have full access to and utilize comprehensive medical management. The present study sought to determine whether food security is related longitudinally to glucose control, over-and-above ongoing medication management, among Type 2 diabetes patients receiving comprehensive care at a Midwestern multi-site federally qualified health centre (FQHC). SUBJECTS/METHODS: In this longitudinal observational study, we completed a baseline assessment of patients' food security (using the US Household Food Security Module), demographics (via Census items), and diabetes history/management (using a structured clinical encounter form) when patients began receiving diabetes care at the health centre. We then recorded those patients' A1C levels several times during a 24-month follow-up period. Three hundred and ninety-nine patients (56% with low food security) had a baseline A1c measurement; a subsample of 336 (median age=52 years; 56% female; 60% Hispanic, 27% African American, and 9% White) also had at least one follow-up A1c measurement. RESULTS: Patients with lower (vs higher) food security were more likely to be on insulin and have higher A1c levels at baseline. Moreover, the disparity in glucose control by food security status persisted throughout the next 2 years. CONCLUSIONS: Although results were based on one multi-site FQHC, potentially limiting their generalizability, they seem to suggest that among Type 2 diabetes patients, low food security directly impairs glucose control-even when patients receive full access to comprehensive medical management-thereby increasing their long-term risks of high morbidity, early mortality, and high health-care utilization and cost.

[Uterine torsion in cattle--therapy and consequences for calf and cow]. / Torsio uteri beim Rind--Therapie und Folgen für das Kalb und die Kuh.

AIM: To summarize the available literature on the therapy of uterine torsion in cattle and the consequences for cow and calf. MATERIAL AND METHODS: Analysis of the literature using electronic libraries (PubMed, Medline), German veterinary medical journals and obstetrical textbooks. RESULTS: The therapy includes the attempt to rotate the uterus back into its physiological position. Direct and indirect methods of retorsion are available and applied according to the case conditions. Subsequently, the extraction of the calf can be performed via vaginal delivery or caesarean section. The presence of uterine torsion always leads to dystocia. Following a successful retorsion, the time and degree of uterine torsion strongly influence the progress of the birth. The prognosis also depends on the aforementioned factors and varies between good to unsuccessful. The vitality of the calf displays great variation depending on the literature (14-90%), however, is generally greater under field than clinical conditions. Focussing on the puerperal development of the cow, all grades from mild irritations of the uterine involution to fatal complications occur. The influence on fertility depends on the progress of the birth and existing secondary complications. The risk for electrolyte disturbances is increased (approximately 50%) as is the risk of birth-associated injuries (approximately 20%). The incidence of placental retention varies widely between different authors (3-52%).

Association of UV radiation with multiple sclerosis prevalence and sex ratio in France.

BACKGROUND: French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor. METHODS: Mean annual and winter (December-March) UVB irradiation values were systematically compared to MS prevalence rates in corresponding regions of France. UVB data were obtained from the solar radiation database (SoDa) service and prevalence rates from previously published data on 2,667 MS cases registered with the national farmer health insurance system, Mutualité Sociale Agricole (MSA). Pearson correlation was used to examine the relationship of annual and winter UVB values with MS prevalence. Male and female prevalence were also analyzed separately. Linear regression was used to test for interaction of annual and winter UVB with sex in predicting MS prevalence. RESULTS: There was a strong association between MS prevalence and annual mean UVB irradiation (r = -0.80, p < 0.001) and average winter UVB (r = -0.87, p < 0.001). Both female (r = -0.76, p < 0.001) and male (r = -0.46, p = 0.032) prevalence rates were correlated with annual UVB. Regression modeling showed that the effect of UVB on prevalence rates differed by sex; the interaction effect was significant for both annual UVB (p = 0.003) and winter UVB (p = 0.002). CONCLUSIONS: The findings suggest that regional UVB radiation is predictive of corresponding MS prevalence rates and supports the hypothesis that sunlight exposure influences MS risk. The evidence also supports a potential role for gender-specific effects of UVB exposure.

Topographical distribution of choroidal naevi in the ocular fundus.

OBJECTIVE: To analyse the topographical distribution of choroidal naevi and to visualise their location in the ocular fundus. METHODS: Data on the size and location of 210 choroidal naevi were converted into a database of two-dimensional retinal charts by means of computer-drawing software. The geometric centre of each lesion was entered into corresponding sectors of the retinal chart. The location of the naevi was computationally visualised by merging the fundus drawings and displaying the number of overlapping lesions on colour-coded contour maps. RESULTS: Five naevi were located exactly between two fundus sectors, and were therefore excluded from the distribution analysis. Ten naevi (5%) were located anterior and 195 (95%) posterior to the equator. A total of 104 naevi (51%) were located in the temporal and 101 (49%) in the nasal hemisphere, and the distribution between the superior and inferior hemisphere was 104 (51%) and 101 (49%), respectively. The distribution did not differ significantly between genders, age groups, or between right and left eyes. More naevi with a diameter of >3 mm were located in the temporal hemisphere (P=0.0004) and anterior to the equator (P=0.006) compared with those with a diameter of

Posterior uveal melanoma. Distribution of the sites of origin and patterns of tumour extent in the ocular fundus.

AIMS: To analyse the distribution of posterior uveal melanoma origin sites and to visualise the patterns of tumour extent in the ocular fundus. METHODS: Data on the size and location of 110 posterior uveal melanomas were converted into a database of two-dimensional retinal charts by means of computer-drawing software. The initiation sites (geometric tumour centres) were entered into corresponding sectors of the retinal chart. The extent of the tumours was visualised by merging the charts and displaying the number of overlapping tumours on colour-coded contour maps. RESULTS: Seventy-one initiation sites (65%) were located in the temporal and 39 (35%) in the nasal hemisphere (p = 0.002). Seventy-six initiation sites (69%) were located posterior and 34 (31%) anterior to the equator. More initiation sites anterior to the equator were observed in large versus small/medium tumours (p = 0.0003), in tumours with a largest basal diameter/height ratio <2 versus > or =2 (p = 0.002), in tumours with a ruptured versus intact Bruch membrane (p = 0.03), in tumours with a mixed/epithelioid versus spindle cell type (p = 0.02) and in tumours leading to metastatic disease (p = 0.003). CONCLUSION: The temporal hemisphere posterior to the equator is the preferential area of melanoma occurrence and growth. For larger and more aggressive tumours, there is a shift towards more peripherally located initiation sites.

Posterior uveal melanoma treated with I-125 brachytherapy or primary enucleation.

PURPOSE: To study the incidence, clinical findings, and tumour characteristics of posterior uveal melanoma in Western Norway, and to report the results of a consistent treatment strategy (I-125 brachytherapy or primary enucleation) over a 13-year period. METHODS: The clinical records of all patients with posterior uveal melanoma referred between January 1993 and December 2005 were reviewed. Clinical data, radiation parameters, visual outcome, and mortality were analysed in a dedicated database. RESULTS: The study included 111 consecutive patients. The annual age-adjusted incidence (per million population) of posterior uveal melanoma was 8.5 for women and 8.9 for men. Fifty-six patients underwent I-125 brachytherapy, 52 were enucleated, and three received no treatment. The median follow-up time was 36 months (mean, 52 months; range, 2 months to 13 years). In the brachytherapy group, two eyes were enucleated owing to tumour recurrence and two because of neovascular glaucoma. A visual acuity of 0.1 or better, present in 87% of the patients before brachytherapy, was retained in 40% after a median follow-up of 61 months. After brachytherapy, the 5- and 10-year melanoma-specific mortality rates were 13.4 and 23.8%, respectively. The corresponding mortality rates for patients treated with primary enucleation were 49.5 and 49.5%. CONCLUSION: After brachytherapy, many patients lost useful vision due to radiation-induced complications. The probability of retaining the eye was high and only two patients experienced recurrent tumour growth. The mortality rates compare well with published series, and the differences in tumour size explain the difference in mortality between the two treatment groups.

Dosimetric verification of a dedicated 3D treatment planning system for episcleral plaque therapy.

PURPOSE: Episcleral plaque therapy (EPT) is applied in the management of some malignant ocular tumors. A customized configuration of typically 4 to 20 radioactive seeds is fixed in a gold plaque, and the plaque is sutured to the scleral surface corresponding to the basis of the intraocular tumor, allowing for a localized radiation dose delivery to the tumor. Minimum target doses as high as 100 Gy are directed at malignant tumor sites close to critical normal tissues (e.g., optic disc and macula). Precise dosimetry is therefore fundamental for judging both the risk for normal tissue toxicity and tumor dose prescription. This paper describes the dosimetric verification of a commercially available dedicated treatment planning system (TPS) for EPT when realistic multiple-seed configurations are applied. MATERIALS AND METHODS: The TPS Bebig Plaque Simulator is used to plan EPT at our institution. Relative dose distributions in a water phantom, including central axis depth dose and off-axis dose profiles for three different plaques, the University of Southern California (USC) #9 and the Collaborative Ocular Melanoma Study (COMS) 12-mm and 20-mm plaques, were measured with a diode detector. Each plaque was arranged with realistic multiple 125I seed configurations. The measured dose distributions were compared to the corresponding dose profiles calculated with the TPS. All measurements were corrected for the angular sensitivity variation of the diode. RESULTS: Single-seed dose distributions measured with our dosimetry setup agreed with previously published data within 3%. For the three multiple-seed plaque configurations, the measured and calculated dose distributions were in good agreement. For the central axis depth doses, the agreement was within 4%, whereas deviations up to 11% were observed in single points far off-axis. CONCLUSIONS: The Bebig Plaque Simulator is a reliable TPS for calculating relative dose distributions around realistic multiple 125I seed configurations in EPT.

Effect of endothelin and BQ123 on ocular blood flow parameters in healthy subjects.

PURPOSE: To characterize the role of the endothelin system in the blood flow control of the optic nerve head and of the choroid in humans. METHODS: Two studies were performed in healthy subjects. Study 1 was a randomized, placebo-controlled, double-masked, balanced, two-way crossover design and study 2 a three way-way crossover design. In study 1 twelve healthy male subjects received endothelin (ET)-1 in stepwise increasing doses of 1.25, 2.5, and 5 ng/kg x min (each infusion step occurred over 20 minutes) coinfused with BQ123 (60 microg/kg x min) or placebo on two different study days. In study 2 twelve healthy male subjects received two doses of BQ123 (60 or 120 microg/kg x min over 60 minutes) or placebo on three different study days. Measurements of optic nerve head blood flow (ONHBF) and choroidal blood flow (ChBF) were performed with laser Doppler flowmetry in both studies. In study 2 mean flow velocity (MFV) of the ophthalmic artery was assessed with Doppler sonography. RESULTS: In study 1, ET-1 significantly decreased ONHBF (-22.8% +/- 4.3% at 5 ng/kg x min, P = 0.003 versus baseline) and ChBF (-21.7% +/- 3.2% at 5 ng/kg x min, P = 0.0001 versus baseline). The effect of the highest administered dose of exogenous ET-1 on ONHBF was significantly attenuated (P = 0.04, ANOVA) by coinfusion of BQ123. Effects of exogenous ET-1 on blood flow (2.5 ng/kg x min ET-1 or higher) also were attenuated in the choroid by coinfusion of BQ123 (ChBF: P = 0.03, ANOVA). In study 2, both dosages of BQ123 significantly increased MFV in the ophthalmic artery (60 microg/kg x min, 12.5% +/- 7.3%; 120 microg/kg x min, 17.2% +/- 9.2%, versus baseline; P = 0.001), but did not change blood flow in the ONH or the choroid. CONCLUSIONS: BQ123 antagonizes the effects of exogenously administered ET-1 on blood flow in the ONH and the choroid. The data indicate, however, that ET-1 does not substantially contribute to the regulation of basal vascular tone in these tissues.

Salvage intravesical therapy with interferon-alpha 2b plus low dose bacillus Calmette-Guerin is effective in patients with superficial bladder cancer in whom bacillus Calmette-Guerin alone previously failed.

PURPOSE: We determined whether combining low dose bacillus Calmette-Guerin (BCG) interferon-alpha 2B would be effective for patients in whom previous BCG failed. MATERIALS AND METHODS: A total of 40 patients in whom 1 (19) or more (21) previous induction courses of BCG failed received 6 to 8 weekly treatments of 1/3 dose (27 mg.) BCG plus 50 million units interferon-alpha 2B. Additional 3 week miniseries of further decreased BCG (1/10, 1/30 or 1/100) titrated to symptoms without changing the interferon-alpha 2B dose were given at 5, 11 and 17 months. In 12 patients a second induction course was given with 1/10 BCG plus 100 million units interferon-alpha 2B. There was multifocal disease in 39 patients, previous BCG had failed within 6 months in 34, disease was aggressive (stage T1, grade 3 or carcinoma in situ in 31, there had been 2 or more previous recurrences in 25 and disease history was greater than 4 years in 13. RESULTS: At a median followup of 30 months 63% and 53% of patients were disease-free at 12 and 24 months, respectively. Patients in whom 2 or more previous BCG courses had failed fared as well as those with 1 failure. Of the 18 failures 14 occurred at the initial cystoscopy evaluation. Of 22 patients initially counseled to undergo cystectomy 12 (55%) are disease-free with a functioning bladder. Combination therapy was well tolerated. CONCLUSIONS: While longer followup and larger multicenter studies are required to validate these encouraging findings, intravesical low dose BCG plus interferon-alpha 2B appears to be effective in many cases of high risk disease previously deemed BCG refractory. However, early failure while on this regimen should be aggressively pursued with more radical treatment options.

Transillumination for accurate placement of radioactive plaques in brachytherapy of choroidal melanoma.

PURPOSE: To present a technique for accurate plaque placement in episcleral brachytherapy of choroidal melanoma. METHODS: The tumor margins are marked on the scleral surface, and a dummy plaque is temporarily sutured to the globe. A fiber optic light pipe is then wedged into the space between the sclera and the plaque. Because of the reflecting inner surface of the plaque, the perimeter of the plaque can easily be observed during indirect ophthalmoscopy as a circle of light surrounding the tumor. By this method, it is possible to determine the exact position of the entire plaque in relation to the tumor and make the necessary adjustments. When the correct position is found, the dummy plaque is replaced by a radioactive plaque. RESULTS: Since 1993, we have routinely used this procedure in episcleral brachytherapy. CONCLUSION: This modified transillumination technique facilitates a correct positioning of episcleral plaques.

Simultaneous, bilateral rhegmatogenous retinal detachment.

PURPOSE: To examine the incidence, the preoperative findings and the surgical outcome of patients presenting with simultaneous, bilateral retinal detachment. METHODS: A retrospective analysis of the medical records of patients undergoing surgery for rhegmatogenous retinal detachment between 1990 and 1998. RESULTS: During this period a total of 827 operations for rhegmatogenous retinal detachment were done in 791 consecutive patients. Eighteen patients (2.3%) had simultaneous, bilateral retinal detachment, giving an annual incidence of 0.35 patients per 100,000 population. They all presented with unilateral symptoms. Compared with the group of unilateral or consecutive, bilateral retinal detachments, patients suffering from simultaneous, bilateral retinal detachments were significantly younger, with a mean age of 40.3 years. Thirteen patients had multiple, round retinal holes associated with lattice degeneration. Sixteen patients were myopic, ranging from -3 to -9.25 diopters. The retina was reattached in 35 (97%) of the 36 eyes operated on during the study period. CONCLUSION: Simultaneous, bilateral retinal detachment is usually found in relatively young, myopic patients with round, atrophic retinal holes, presenting with unilateral visual symptoms.

In vivo measurement of solute transport rates in a bioartificial organ.

A radioactive tracer technique was used to evaluate the in vivo mass transfer properties of a tissue engineered bioartificial organ. To obtain these measurements, bioartificial organs were first implanted in ten rats and allowed to vascularize for 4 weeks. After vascularization, radioactive inulin was placed within the cell chamber of the device. Following the addition of tracer, blood samples were taken over a 4-h time period and inulin levels were determined. The results of these experiments were interpreted using a compartmental model that describes the transport of inulin from the cell chamber, across the immunoisolation membrane, and into the neovascularized region contained within the adjacent scaffold material. Nonlinear regression analysis of the plasma inulin levels using a four-compartment pharmacokinetic model provided estimates of the membrane permeability, the product of the capillary wall surface area and capillary permeability, and the glomerular filtration rate (GFR). The permeability of the membrane was found to be 3.50 x 10(-5) +/- 1.15 x 10(-5) cm/sec (95% confidence interval, n = 10), which compares favorably to previous in vitro permeability data for this membrane. The capillary wall permeability was found to be 0. 0087 6 0.0029 cm(3)/sec/100 g of tissue. This compares well to a reported value for inulin of 0.01 cm(3)/sec/100 g of tissue. The GFR was found to be 0.44 +/- 0.07 ml/h/g BW, which compares well with a reported value of 0.40 ml/hr/g BW. The inulin tracer technique reported here is a useful tool for assessing the in vivo transport characteristics of a bioartificial organ as well as the vascularization within tissue engineered structures.

Expression of factor VIII-related antigen in human aqueous drainage channels.

PURPOSE: Previous studies have indicated that there are preformed channels at the inner aspect of the anterior sclera, capable of draining fluid from the suprachoroidal space into scleral veins. The aim of this study was to characterize the cellular lining of these channels, and to compare it with the endothelium of Schlemm's canal, the collector channels and the scleral blood vessels. METHODS: Histological sections from the angular region of human eyes were prepared by an immunoperoxidase method to evaluate the expression of factor VIII-related antigen in different aqueous drainage channels. RESULTS: The cellular lining of the scleral channels showed a weak immunostaining to factor VIII-related antigen. Factor VIII-related antigen was also detected in the endothelium of the collector channels and Schlemm's canal. CONCLUSION: The positive immunoreaction to factor VIII-related antigen indicates that the previously described scleral channels, the collector channels and Schlemm's canal are all lined by an endothelium derived from a vascular origin.

Iris cyst associated with topical administration of latanoprost.

PURPOSE: To report an adverse side effect associated with topical latanoprost usage. METHOD: Case report. A 76-year-old woman with primary open-angle glaucoma developed an iris cyst 5 weeks after beginning treatment with latanoprost. Clinical examinations and slit-lamp photographs were performed. RESULTS: Latanoprost was discontinued. Periodic examinations disclosed that the iris cyst gradually diminished and finally disappeared within 3 weeks. CONCLUSION: The formation of an iris cyst is a possible complication of topical latanoprost therapy.

Light microscopy of uveoscleral drainage routes after gelatine injections into the suprachoroidal space.

PURPOSE: To visualize the suprachoroidal space and to study the morphology of possible uveoscleral drainage routes in the human eye. METHODS: Indian ink stained gelatine was injected directly into the suprachoroidal space of 7 human donor eyes. Those quadrants where gelatine appeared in the episcleral venous network were cut in their entirety in consecutive sections and examined by light microscopy. RESULTS: Gelatine was observed in the connective tissue surrounding scleral vessels and nerves. Gelatine was also traceable in fine, endothelium-lined channels at the inner aspect of the anterior sclera. These channels seemed to originate at the inner surface of the sclera, close behind the scleral spur, and communicate with the intrascleral venous plexus. CONCLUSION: Fluid is drained from the suprachoroidal space through the perivascular and perineural spaces of scleral blood vessels and nerves. In addition, this study indicates that there are preformed channels at the inner aspect of the anterior sclera, capable of draining fluid directly into scleral veins.

Exudative retinal detachment in nanophthalmos.

PURPOSE: To report the treatment of exudative retinal detachment in a patient with nanophthalmos. METHODS: A 46-year-old man with bilateral nanophthalmos suffered from acute angle-closure glaucoma in his left eye. The first day after a peripheral iridectomy an exudative retinal detachment was observed. Two months later a partial thickness sclerectomy with a central sclerostomy, covered by a thin film of absorbable gelatine, was performed in each quadrant of the left eye. RESULTS: The retinal detachment gradually resolved and after eight months the retina was completely reattached. Vision, which had been limited to hand movements, improved to 6/18 with correction. CONCLUSION: Scleral resections are effective in the treatment of nanophthalmic retinal detachment. The use of absorbable gelatine film to cover the sclerectomized area may prevent regeneration of scleral tissue and recurrence of the exudative retinal detachment.

Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the pig eye.

Eyes from pigs were studied by corrosion casting technique. Batson's mixture No. 17 (methyl methacrylate) was injected through a sclerotomy into the suprachoroidal space. Following polymerisation of the injected mixture the surrounding tissue was dissolved with 10% natrium hydroxide. Macroscopic and scanning electron microscopic findings in casts of the suprachoroidal space are presented. The outer (scleral) surface of the casts was rough, with a fish-scale-like appearance caused by fine lamellas between the sclera and choroid, running from the inner layers of the sclera traversing the space anteriorly to the choroid. Frequently, irregular, Y-shaped branches deriving from the outer surface of the casts were observed. They corresponded to the perivascular space of the vortex veins and represent a possible uveoscleral drainage route for aqueous humour.