Machine Learning to Predict Prostate Artery Embolization Outcomes.

PURPOSE: This study leverages pre-procedural data and machine learning (ML) techniques to predict outcomes at one year following prostate artery embolization (PAE). MATERIALS AND METHODS: This retrospective analysis combines data from the UK-ROPE registry and patients that underwent PAE at our institution between 2012 and 2023. Traditional ML approaches, including linear regression, lasso regression, ridge regression, decision trees and random forests, were used with leave-one-out cross-validation to predict international prostate symptom score (IPSS) at baseline and change at 1 year. Predictors included age, prostate volume, Qmax (maximum urinary flow rate), post-void residual volume, Abrams-Griffiths number (urodynamics score) and baseline IPSS (for change at 1 year). We also independently confirmed our findings using a separate dataset. An interactive digital user interface was developed to facilitate real-time outcome prediction. RESULTS: Complete data were available in 128 patients (66.7 ± 6.9 years). All models predicting IPSS demonstrated reasonable performance, with mean absolute error ranging between 4.9-7.3 for baseline IPSS and 5.2-8.2 for change in IPSS. These numbers represent the differences between the patient-reported and model-predicted IPSS scores. Interestingly, the model error in predicting baseline IPSS (based on objective measures alone) significantly correlated with the change in IPSS at 1-year post-PAE (R2 = 0.2, p < 0.001), forming the basis for our digital user interface. CONCLUSION: This study uses ML methods to predict IPSS improvement at 1 year, integrated into a user-friendly interface for real-time prediction. This tool could be used to counsel patients prior to treatment.

The effect of size ratio on the sphere structure factor in colloidal sphere-plate mixtures.

Binary mixtures of colloidal particles of sufficiently different sizes or shapes tend to demix at high concentration. Already at low concentration, excluded volume interactions between the two species give rise to structuring effects. Here, a new theoretical description is proposed of the structure of colloidal sphere-plate mixtures, based on a density expansion of the work needed to insert a pair of spheres and a single sphere in a sea of them, in the presence or not of plates. The theory is first validated using computer simulations. The predictions are then compared to experimental observations using silica spheres and gibbsite platelets. Small-angle neutron scattering was used to determine the change of the structure factor of spheres on addition of platelets, under solvent contrast conditions where the platelets were invisible. Theory and experiment agreed very well for a platelet/sphere diameter ratio D∕d = 2.2 and reasonably well for D∕d = 5. The sphere structure factor increases at low scattering vector Q in the presence of platelets; a weak reduction of the sphere structure factor was predicted at larger Q, and for the system with D∕d = 2.2 was indeed observed experimentally. At fixed particle volume fraction, an increase in diameter ratio leads to a large change in structure factor. Systems with a larger diameter ratio also phase separate at lower concentrations.

Vaginal hysterectomy for pelvic organ prolapse in Nepal.

BACKGROUND: UVP is a significant Public Health Problem in Nepal. This problem is mainly prevalent in rural areas where the women are socio--economically less privileged and cannot afford the costs of treatment. OBJECTIVE: An analysis of peri operative and post operative complications of vaginal hysterectomies for pelvic organ prolapse. MATERIALS AND METHODS: A hospital based prospective study was carried out in the department of obstetrics and gynaecology, NGMC followed up from the time of operation to time of discharge. RESULTS: 632 cases underwent vaginal hysterectomy with financial support from UNFPA. There were no operative complications. The most common post operative complications as noted were retention of urine, pelvic infection & pelvic abscess. In two cases laparotomy was done for haemoperitoneum. Pelvic abscess was drained vaginally. Mortality was nil. CONCLUSION: Proper screening before operation is the key to reduce operative as well as peri operative complications.

Distribution of Legionella pneumophila serogroups, monoclonal antibody subgroups and DNA sequence types in recent clinical and environmental isolates from England and Wales (2000-2008).

Clinical isolates of Legionella pneumophila, obtained from 167 patients, who acquired their illness in the community in England and Wales between January 2000 and March 2008, were compared with 276 environmental isolates of L. pneumophila obtained over the same period as part of the routine sampling of 'managed' water systems. The 443 isolates were typed by monoclonal antibody (mAb) subgrouping and the internationally standardised, seven-gene loci, sequence-based typing (SBT) scheme of the European Working Group for Legionella Infections (EWGLI). Of the clinical isolates, 97.6% were L. pneumophila serogroup (sgp) 1, compared with only 55.8% of environmental isolates (P = 0.0002); 91.6% were subgrouped as mAb3/1+ve, compared with only 8.3% of environmental isolates (P < 0.0001). The isolates were very diverse, with SBT identifying 111 sequence types (STs) (index of diversity [IOD] 0.954). Among the clinical isolates, 42 ST were seen, with one (ST47) accounting for 25.7% and three (ST47, ST37 and ST62) accounting for 46.1% of all isolates. Eighty-two STs were identified among the environmental isolates, with two (ST1 and ST79) accounting for 34.1% of these. Comparison of the STs seen among clinical and environmental isolates showed that there was very little overlap between the two populations (P < 0.0001), with common clinical strains found in the environment very infrequently: 0.4, 0.7 and 0% (ST47, ST37 and ST62, respectively), and common environmental strains rarely causing disease: 4.8 and 1.2% (ST1 and ST79, respectively). Combining phenotypic and genotypic data identified 144 phenons (IOD 0.970); 52 among clinical isolates and 101 among environmental isolates. The most abundant clinical strain, mAb 'Allentown' ST47, accounted for 22.8% of cases, but was only found once in the environment. Conversely, mAb 'Oxford/OLDA' ST1 was the most common environmental strain (17.0%), but only caused two infections. A review of the published data shows that mAb 'Allentown' ST47 is also an important cause of infection in France and possibly in the Netherlands. However, it was not found in a large study of German clinical isolates. This study confirms previous work showing that just a few strains of L. pneumophila cause the majority of community-acquired Legionella infection in England and Wales, and that these clinically significant strains are only rarely found in managed water systems. These data suggest that knowing which particular strain is present in an environment might be at least as important as knowing the quantity in which legionellae are present.

Comparison of clinical and environmental isolates of Legionella pneumophila obtained in the UK over 19 years.

Between January 1980 and December 1998, 3458 cases of Legionnaires' disease were reported to the national surveillance scheme in England and Wales. Of these, 463 (13.4%) were reported as proven by culture and isolation of Legionella spp., with 96.3% being Legionella pneumophila. Serogroup (Sgp), monoclonal antibody (mAb) subgrouping and restriction fragment length polymorphism (RFLP) analysis data were obtained for 321 (69.3%) of these, of which 284 were classified as being unrelated to any other isolate in the study. Typing data were also available for 117 unrelated environmental isolates of L. pneumophila obtained from England and Wales, giving a total of 401 unrelated isolates in the study. Of the clinical isolates, 88.0% were Sgp1, compared with only 42.7% of environmental isolates (p <0.001); 79.6% of clinical isolates were subgrouped as mAb2+, compared with only 12.8% of environmental isolates (p <0.001). RFLP typing identified 67 types among the 401 isolates, with clinical isolates showing significantly less diversity than environmental isolates (index of diversity (IOD) 0.944 vs. 0.958; p <0.05), with three RFLP types (1, 5 and 14) accounting for 40.0% of all clinical isolates. Combining the phenotypic and genotypic data resulted in 173 distinct phenons, with clinical isolates showing significantly less diversity than environmental isolates (IOD 0.964 vs. 0.996; p <0.01). Three phenons accounted for 30% of all clinical isolates. These data strongly suggest that some strains of L. pneumophila are more likely to cause human infection than would be expected from their distribution in the environment.

Mechanism of spasmolytic activity of a fraction of Sarcostemma brevistigma Wight.

The effect of chloroform soluble fraction (F-A) of twigs of Sarcostemma brevistigma on contractions induced by KCl, histamine, and acetylcholine in the isolated guinea pig ileum and taenia coli smooth muscles has been evaluated. F-A (19.5 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 87.6% in the isolated guinea pig ileum. In the isolated guinea pig ileum, F-A (64.3 and 59.2 microg/ml) significantly inhibited the contractions induced by acetylcholine and histamine to the extent of 85 and 83% respectively. In the isolated guinea pig taenia coli, F-A (65.2 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 96.0%. The inhibitory effect of F-A (40 microg/ml) on the isolated guinea pig taenia coli was reduced by Bay K 8644 (10(-6) M) to the extent of 61.6 from 73.6%. These results suggest that the F-A may exhibit smooth muscle relaxant activity by blocking the Ca2+ channels.

Robustness of protein folding kinetics to surface hydrophobic substitutions.

We use both combinatorial and site-directed mutagenesis to explore the consequences of surface hydrophobic substitutions for the folding of two small single domain proteins, the src SH3 domain, and the IgG binding domain of Peptostreptococcal protein L. We find that in almost every case, destabilizing surface hydrophobic substitutions have much larger effects on the rate of unfolding than on the rate of folding, suggesting that nonnative hydrophobic interactions do not significantly interfere with the rate of core assembly.

Evaluation of the detectability of breast cancer lesions using a modified anthropomorphic phantom.

UNLABELLED: During the development and characterization of imaging technology or new imaging protocols, it is usually instructive to perform phantom experiments. Often, very simplified forms of the realistic patient anatomy are used that may be acceptable under certain conditions; however, the implications for patient studies can be misleading. This is particularly true in breast and axillary node imaging. The complexities presented by the anatomy, variable object scatter, attenuation and inhomogeneous distribution of activity in this upper thoracic region provide a significant challenge to the imaging task. METHODS: A tissue-equivalent anthropomorphic phantom of the thorax (Radiology Support Devices, Inc., Long Beach, CA) containing fillable cavities and organs was modified for the studies. The phantom was filled with realistic levels of FDG activity and scanned on a Siemens ECAT HR+ whole-body PET scanner. Breast attachments containing 2.0- and 2.55-cc lesions with lesion-to-background ratios of 5:1 and 7:1, respectively, were imaged. Scatter and attenuation effects were analyzed with various experimental setups. A lymph node experiment and a multibed position whole-phantom scan also were performed to illustrate the extent to which the phantom represents the human thorax. RESULTS: Regions of interest were drawn on the lesions as well as the background breast tissue in all studies. It was found that the signal-to-noise ratio decreased 65% when a more realistic phantom (lesions plus breasts plus thorax, all containing activity) was used, as compared to a simple phantom (lesions plus breasts containing activity; no thorax), due to the effects of increased scatter and attenuation. A 23% decrease in the contrast also was seen from the scan of the more realistic phantom due to surrounding activity from nearby organs such as the heart, as well as an increase in the volume of attenuating media. CONCLUSION: This new phantom allows us to more realistically model the conditions for breast and lymph node imaging, leading to preclinical testing that will produce results that better approximate those that will be found in vivo. The phantom will be a valuable tool in comparing different imaging technologies, data collection strategies and image reconstruction algorithms for applications in breast cancer using PET, SPECT or scintimammography systems.

Improved signal-to-noise in PET activation studies using switched paradigms.

UNLABELLED: PET activation studies employing the autoradiographic technique and 15O-water or 15O-butanol use the difference between images acquired under baseline conditions and during activation to detect focal changes in cerebral blood flow which occur upon stimulus presentation. Typically, the activating task or baseline conditions are maintained throughout the entire imaging period. Simulations of the kinetics of these freely diffusible tracers suggest there may be an advantage to switching between activation and baseline conditions during the course of the study which results in images which maximize the difference signal rather than seeking to quantitate blood flow. We examine the potential of these switched protocols to increase signal-to-noise (S/N) in PET activation studies. METHODS: We examined S/N in activation studies using both-standard and switched paradigms with a simple switched protocol and dynamic three-dimensional PET data from human subjects. With tracer kinetic simulations, we investigated the sensitivity of the S/N gain to factors such as the shape of the input function, the time at which the conditions are switched and the magnitude of the activation. RESULTS: In human studies of activation sites in the visual cortex, primary motor and premotor areas, S/N improvements of 20%-30% were detected using the switched paradigms. Simulations show that this gain is virtually independent of activation magnitude and that there is a broad time window of 20 sec for making the switch between conditions. To obtain the highest S/N gain, a rapid bolus injection is required. CONCLUSION: Switched paradigms have the potential to significantly increase S/N in PET activation studies. In human studies, the S/N increase averaged 25% which is equivalent to increasing the number of counts collected by 50%. Switched paradigms can be used to maximize the difference signal in many activation studies, and do not preclude the absolute quantitation of blood flow using the standard autoradiographic technique.

Beemer-Langer syndrome with manifestations of an orofaciodigital syndrome.

We report on an infant girl with hydrops, macrocephaly, high forehead, flat face, hypertelorism, broad nasal bridge, median cleft lip and alveolar ridge, grooved palate, accessory frenula, small tongue, milia, severe rib and limb shortness, brachydactyly, talipes equinovarus, Dandy-Walker malformation, accessory spleen, unfixed mesentery, ectopic pancreas, and renal cysts. This patient resembles seven previously reported patients with the Beemer-Langer syndrome, a distinct lethal short rib syndrome characterized by hydrops, markedly short ribs and limbs, median cleft lip with or without cleft palate, flat face, and macrocephaly. Polydactyly is usually absent. Our patient's oral anomalies suggest an orofaciodigital syndrome, but the severe rib and limb shortness distinguish it from those disorders.

Pulmonary yellow hyaline membranes in neonates.

The recent increase in the occurrence of pulmonary yellow hyaline membranes correlates with improved therapy for premature infants with the respiratory distress syndrome and with their prolonged survival. We compared the clinicopathologic features in 54 cases with pulmonary yellow hyaline membranes with those in 56 cases with conventional hyaline membranes seen during the same interval at Magee-Womens Hospital. Kernicterus, intraventricular hemorrhage, intrahepatic bile stasis, pulmonary hemorrhages, and disseminated intravascular coagulation were significantly frequent in the yellow hyaline membrane group. Clinical problems of hypoglycemia, hypocalcemia, jaundice, and endotracheal hemorrhages and also treatment with endotracheal intubation, ventilatory assistance, and phototherapy were much more common in the yellow hyaline membrane cases. The yellow pigment was identified as unconjugated bilirubin by histochemical and biochemical techniques. A plausible hypothesis for the pathogenesis is presented wherein intrapulmonary hemorrhages lay an important role. The frequent association of yellow membranes and kernicterus in premature infants at relatively low serum levels of bilirubin is significant.

Morphologic anomalies in triploid liveborn fetuses.

Analysis of the morphologic features of 43 complete and 11 mosaic triploid infants delivered at or after 22 weeks of gestation revealed, in addition to well-delineated gross features, a number of new or previously little emphasized histopathologic features. These included testicular Leydig cell hyperplasia, increased levels of hematopoiesis, and ovarian, adrenal, and pulmonary hypoplasia. Some of these findings appeared to be linked to partial hydatidiform mole replacing the normal placenta, which was present in about 70 per cent of the triploid cases. It is important to recognize the breadth of the triploidy spectrum, which ranges from near normalcy to multisystem involvement, and to pay special attention to the placenta. The importance of correct morphologic diagnosis of triploidy is stressed in view of the fact that its occurrence apparently does not prejudice the future reproductive performance of the parents.

Comparison of the Vi indirect fluorescent antibody test with the Widal agglutination method in the serodiagnosis of typhoid fever.

The indirect fluorescent antibody test using a whole Salmonella typhi Vi suspension as the antigen has been evaluated for the diagnosis of typhoid fever. Results using sera from 140 patients with S typhi infections proved on culture show the test to have good sensitivity. The test appears to be highly specific, although it has not yet been investigated with respect to typhoid vaccination or in the context of infections due to salmonellas other than S typhi.

Ascending transcervical herpes simplex infection with intact fetal membranes.

A case of herpes simplex infection in the placenta and in an immature infant delivered to a mother with proved genital herpes infection is discussed. Infection occurred without premature rupture of membranes. Viral transmission could be attributed to ascending transcervical infection based on evidence of necrotizing chorioamnionitis in absence of villitis plus extensive and severe involvement of the skin and lungs. Such distinct documentation of transcervical infection in the presence of intact fetal membranes makes it obvious that delivery by cesarean section cannot prevent all cases of neonatal herpes infection.

Survey of Bartonella species infecting intradomicillary animals in the Huayllacallán Valley, Ancash, Peru, a region endemic for human bartonellosis.

The natural cycle of Bartonella bacilliformis remains uncertain, and the suspected existence of animal reservoirs for the bacterium has never been convincingly demonstrated. We conducted a survey of Bartonella species infecting intradomicillary animals in a bartonellosis-endemic region of Peru, obtaining blood from 50 animals living in the homes of 11 families whose children had recently had bartonellosis. Bartonella-like bacteria were recovered from four of nine small rodents included in the study, but from none of the 41 domesticated animals. Identification and comparison of these isolates, and two Bartonella-like isolates obtained from Phyllotis mice in a different endemic region of Peru using serologic and genotypic methods indicated that although none were strains of B. bacilliformis, five were probably representatives of three previously unrecognized Bartonella species and one was a likely strain of the pathogenic species B. elizabethae.

Further evidence that genotypically closely related strains of Legionella pneumophila can express different serogroup specific antigens.

The relationship between serogroup and genotype of Legionella pneumophila strains was investigated by restriction fragment length polymorphism (RFLP) typing with a previously standardised method. Of the 51 RFLP types identified, 19 comprised strains of more than one serogroup. Several RFLP types included strains of five or more serogroups. To determine if sharing the same RFLP type indicates that strains are genotypically indistinguishable or merely that they are superficially similar, 31 strains were selected for further analysis with an extended range of restriction endonucleases and nucleic acid probes. In some cases, strains of a particular RFLP type were indistinguishable, while in others the restriction fragment patterns showed minor differences. It is possible that in the latter case the strains are diverging representatives of a parent clone. We conclude that analysis of restriction fragment patterns, either probed or unprobed, provides a more accurate measure of the ancestral relationship between strains than can be obtained with serological methods.

Design and evaluation of an LSO PET detector for breast cancer imaging.

Functional imaging with positron emission tomography (PET) may be a promising technique in conjunction with x-ray mammography for breast cancer patient management. Conventional whole body PET scanners provide metabolic images of breast cancer patients with several shortcomings related to the general-purpose nature of these systems. In whole body scanners, the detectors are typically 20-30 cm away from the breast or axilla, reducing sensitivity, and these scanners have relatively large detector elements (> 4 mm), limiting spatial resolution. Dedicated PET systems for breast imaging aim to overcome these limitations and improve the overall diagnostic quality of the images by bringing the detectors closer to the area to be imaged, thereby improving sensitivity, and by using smaller detector elements to improve the spatial resolution. We have designed and developed a modular PET detector that is composed of a 9x9 array of 3x3x20 mm3 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to an optical fiber taper, which in turn is coupled to a Hamamatsu R5900-C8 position-sensitive photomultiplier tube. These detectors can be tiled together without gaps to construct large area detector arrays to form a dedicated PET breast cancer imaging system. Two complete detector modules have been built and tested. All detector elements are clearly visualized upon flood irradiation of the module. The intrinsic spatial resolution (full-width at half-maximum) was measured to be 2.26 mm (range 1.8-2.6 mm). The average energy resolution was 19.5% (range 17%-24%) at 511 keV. The coincidence time resolution was measured to be 2.4 ns. The detector efficiency for 511 keV gamma rays was 53% using a 350 keV energy threshold. These promising results support the feasibility of developing a high resolution, high sensitivity dedicated PET scanner for breast cancer applications.

Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging.

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.

Oligohydramnios and fatal pulmonary hypoplasia without amnion nodosum.

Two cases of fatal pulmonary hypoplasia associated with hydrorrhea gravidarum are presented. Amnion nodosum was present in one case but not the other. The pathogenesis of amnion nodosum is reviewed, and the clinical implications of this pathologic finding are discussed in relation to whether the underlying pathology is renal agenesis or amniorrhea.

The significance of atypical cervical smears.

The significance of and approach to cervical smears showing cytologic atypia without dyskaryosis remains controversial. A review of 139 colposcopies performed for atypical cytology revealed cervical intraepithelial neoplasia (CIN) in 25%. Of the CIN found, 85% was CIN I and 15%, II. No case of more advanced disease was found. The type and severity of the cytologic atypia correlated with the presence of CIN. However, all degrees of atypia were found to have a significant association with CIN, and the degree of cytologic atypia therefore cannot be used to exclude colposcopy in any women with atypical smears. This study suggested that cytologic atypia is an expression of early CIN, and the results support our endorsement of routine colposcopy in the evaluation of women with persistent atypia.