Evaluation of ocular and systemic endpoints after radiation of posterior uveal melanoma - A systematic review and meta-analysis.

Background: Due to the large number of radiotherapeutic options for treatment of posterior uveal melanoma (UM), advantages of each option regarding important clinical endpoints have yet to be determined. Therefore, objective of this systematic review was to analyze the numerous pro- and retrospective cohort studies focusing on the efficacy of different radiotherapeutic options for UM in adults, considering local tumor control, overall survival, visual acuity, eye preservation, metastasis, radiation side effects and dose rates. Methods: The Review was performed based on the Cochrane Handbook of Systematic Reviews. The PubMed database was searched for studies published from January 1st, 2000, up to December 31st, 2021. Research, study selection and critical appraisal was performed by two reviewers. The risk of bias assessment was performed through the revised Cochrane risk of bias tools RoB 2 and ROBINS-I. A meta-analysis of proportions was performed using R (R version 4.1.3, library: meta, procedure: metaprop). This systematic review was registered with Prospero (ID CRD42022311758). Results: Of 4886 studies identified in the database, a total of 20 studies with 4979 participants were included in the qualitative synthesis. Through critical appraisal with ROBINS-I and RoB 2, studies received a 'moderate', 'serious' or 'some concerns' overall risk of bias. Heterogeneity analysis allowed for meta-analysis of proportion of 3 outcome-therapy combinations: local tumor control with I-125 Brachytherapy (proportion: 0.94, CI 95 %: 0.91-0.98), local tumor control with proton therapy (proportion: 0.96, CI 95 %: 0.92-1.00) and eye preservation with I-125 brachytherapy (proportion: 0.91, CI 95 %: 0.88-0.93). This shows local tumor control to be at 94 % with I-125 brachytherapy and at 96 % with proton therapy, as well as an eye preservation rate of 91 % with I-125 brachytherapy. Discussion: The evaluation of outcomes of radiotherapy in UM is limited because of missing data on radiation doses as well as great heterogeneity of study protocols. Radiation therapy outcomes are so far not comparable. Therefore, we recommend for upcoming studies on this topic to provide the biological effective dose (BED) or the equivalent dose in 2 Gy fractions (EQD2) per eye structure, thereby enabling a comparison of outcomes of different forms of radiation therapy.

Navigating noisy waters: A review of field studies examining anthropogenic noise effects on wild fisha).

Anthropogenic noise is globally increasing in aquatic ecosystems, and there is concern that it may have adverse consequences in many fish species, yet the effects of noise in field settings are not well understood. Concern over the applicability of laboratory-conducted bioacoustic experiments has led to a call for, and a recent increase in, field-based studies, but the results have been mixed, perhaps due to the wide variety of techniques used and species studied. Previous reviews have explored the behavioral, physiological, and/or anatomical costs of fish exposed to anthropogenic noise, but few, if any, have focused on the field techniques and sound sources themselves. This review, therefore, aims to summarize, quantify, and interpret field-based literature, highlight novel approaches, and provide recommendations for future research into the effects of noise on fish.

Infrared photoconductivity and photovoltaic response from nanoscale domains of PbS alloyed with thorium and oxygen.

Thin films of lead sulfide alloyed with thorium and oxygen were deposited on GaAs substrates and processed to produce a photo-diode structure. Structural, optical and electrical characterizations indicate the presence of small nanoscale domains (NDs) that are characterized by dense packaging, high quality interfaces and a blue-shift of the energy bandgap toward the short wavelength infrared range of the spectrum. Photocurrent spectroscopy revealed a considerable photoconductivity that is correlated with excitation of carriers in the NDs of lead sulfide alloyed with thorium and oxygen. Furthermore, the appearance of a photovoltaic effect under near infrared illumination indicates a quasi-type II band alignment at the interface of the GaAs and the film of NDs.

Sirolimus and tuberous sclerosis-associated renal angiomyolipomas.

Tuberous sclerosis, caused by germline mutations in the TSC1 or TSC2 genes, is associated with aberrant upregulation of the mammalian target of rapamycin (mTOR) signalling pathway, resulting in growth of tumours, including renal angiomyolipomas (AMLs). AMLs may cause hypertension, renal failure and spontaneous life-threatening haemorrhage. Previously, invasive interventions were required to treat AMLs. More recently, mTOR inhibitors have been used as molecularly targeted treatment to treat AMLs. We present here the case of a paediatric patient with TSC in whom sirolimus has been used successfully to halt growth of renal AMLs.

A case of near-drowning: a case for routine cerebral monitoring.

UNLABELLED: A 6-week-old infant presenting with near-drowning was medically paralysed and ventilated on admission. Status epilepticus was found on cerebral function monitoring, without which the diagnosis would have been missed or delayed for many hours. This case illustrates the value of cerebral function monitoring for patients in intensive care, where clinical signs of seizure activity are frequently masked by paralysis and sedation. CONCLUSION: Limited availability of electroencephalogram (EEG) and cerebral function monitoring (CFM) in paediatric intensive care may inadvertently delay diagnosis and appropriate treatments and so adversely affect outcomes. We propose that round-the-clock cerebral function and/or EEG monitoring should be available in all centres that provide paediatric intensive care.

Respecting autonomy in young people.

Paediatricians have a duty to protect the life and health of their patients and to respect their autonomy. Usually, there will be no conflict between these duties. Both children and parents want effective care and agree to the medical interventions that that are most likely to provide it. However, when children refuse or resist such interventions, it may be unclear when the duty to protect trumps the duty to respect. This is because children may have differing levels of autonomy, sometimes making them competent to make medical decisions for themselves and at other times not. Further, there may be conflict between the children and their parents in such circumstances. Children may refuse treatments that parents desire or vice versa. Sometimes paediatricians may agree with the child in the face of legal powers of parental guardianship. At other times they may agree with the parents, facing the prospect of forcing treatment on an unwilling child with potentially devastating psychological consequences. This paper will explore this potential ethical and legal minefield by evaluating some practical clinical cases based on the experiences of the primary author. It provides a range of examples of these different types of conflicts, including especially problematic "hard cases" that concern the withdrawal of life-sustaining treatment and child protection. The goal of the article is not simply to morally and legally outline the boundaries of such tensions in paediatric care. It also provides concrete advice about how they should best be resolved in everyday clinical practice.

Estimation of the Rigid-Body Motion from Three-Dimensional Images Using a Generalized Center-of-Mass Points Approach.

We present an analytical method for the estimation of rigid-body motion in sets of three-dimensional SPECT and PET slices. This method utilizes mathematically defined generalized center-of-mass points in images, requiring no segmentation. It can be applied to compensation of the rigid-body motion in both SPECT and PET, once a series of 3D tomographic images are available. We generalized the formula for the center-of-mass to obtain a family of points co-moving with the object's rigid-body motion. From the family of possible points we chose the best three points which resulted in the minimum root-mean-square difference between images as the generalized center-of-mass points for use in estimating motion. The estimated motion was used to sum the sets of tomographic images, or incorporated in the iterative reconstruction to correct for motion during reconstruction of the combined projection data. For comparison, the principle-axes method was also applied to estimate the rigid-body motion from the same tomographic images. To evaluate our method for different noise levels, we performed simulations with the MCAT phantom. We observed that though noise degraded the motion-detection accuracy, our method helped in reducing the motion artifact both visually and quantitatively. We also acquired four sets of the emission and transmission data of the Data Spectrum Anthropomorphic Phantom positioned at four different locations and/or orientations. From these we generated a composite acquisition simulating periodic phantom movements during acquisition. The simulated motion was calculated from the generalized center-of-mass points calculated from the tomographic images reconstructed from individual acquisitions. We determined that motion-compensation greatly reduced the motion artifact. Finally, in a simulation with the gated MCAT phantom, an exaggerated rigid-body motion was applied to the end-systolic frame. The motion was estimated from the end-diastolic and end-systolic images, and used to sum them into a summed image without obvious artifact. Compared to the principle-axes method, in two of the three comparisons with anthropomorphic phantom data our method estimated the motion in closer agreement to than of the Polaris system than the principal-axes method, while the principle-axes method gave a more accurate estimation of motion in most cases for the MCAT simulations. As an image-driven approach, our method assumes angularly complete data sets for each state of motion. We expect this method to be applied in correction of respiratory motion in respiratory gated SPECT, and respiratory or other rigid-body motion in PET.

The importance of acknowledging clinical uncertainty in the diagnosis of epilepsy and non-epileptic events.

BACKGROUND: Failure to recognise diagnostic uncertainty between the epilepsies and non-epileptic events may be a factor in high rates of misdiagnosis. AIMS: To explore the results of acknowledging diagnostic uncertainty in a cohort of children presenting with paroxysmal events. METHODS: Children (29 days-16th birthday) with new presentations of paroxysmal disorders were ascertained through outpatients, admissions, and accident and emergency over a two year period in a district hospital with a catchment population of 500,000. Cases were classified by diagnosis at entry and 6-30 months later. A random selection of cases was independently assessed. RESULTS: A total of 684 cases were ascertained. Attacks were initially classified as febrile seizures (n = 212), acute symptomatic epileptic seizures (n = 5), epilepsies (n = 83), unclassified (possible epilepsy) (n = 90), isolated epileptic seizures (n = 51), and non-epileptic events (n = 243). Case review enabled reclassification of 61 of those initially unclassified--31 to an epilepsy and 27 to non-epileptic events. In 29 the final diagnosis was never clarified. These were 23 cases with confusing or absent histories and six with short lived seizure clusters. Prognosis for these 29 cases was good; 75% had been discharged. None were on long term medication. The diagnosis in the 131 cases confirmed as epilepsy was stable. Independent review of a random sample showed full concordance with one neurologist and 20% uncertainty with another. CONCLUSION: In addition to definite epilepsy or non-epileptic events it is helpful to recognise a group of cases where the diagnosis is uncertain-unclassified paroxysmal events. Reassessment of these cases enables accurate diagnosis and may prevent a hasty and incorrect diagnosis of epilepsy.

Cervical schistosomiasis, human papilloma virus (HPV), and human immunodeficiency virus (HIV): a dangerous coexistence or coincidence?

BACKGROUND: Female genitourinary schistosomiasis (FGS) is widespread in endemic areas causing significant morbidity and mortality. Recent data suggest that FGS of the cervix not only is considered a risk factor for contracting different sexually transmitted diseases (STD), but also plays a significant role in modifying the natural history and immunological response to those infections, in particular HIV and HPV. CASE REPORT: A 32-year-old female from Zambia, who was recently diagnosed with HIV and high-grade dysplasia with koilocytosis on cervical Pap smear, underwent cervical conization which confirmed moderate cervical dysplasia and also revealed the presence of viable and nonviable schistosoma eggs in cervical stroma. Four different HPV types were isolated by PCR, including one "low-risk" (type 6) and three "high-risk" types (types 45,56, and 58). CONCLUSION: The presence of HPV, HIV infection, and cervical schistosomiasis in our patient is likely more than coexistence of multiple agents in the same milieu as cervical schistosomiasis increase susceptibility for other STDs including HIV and HPV. Therefore, in patients with schistosomiasis, immediate treatment for schistosomiasis and additional testing for HIV and HPV is warranted.

P504S immunohistochemical detection in 405 prostatic specimens including 376 18-gauge needle biopsies.

P504S is a recently described, prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. A recent study has shown that immunohistochemical detection of P504S gene product is a sensitive and specific marker of prostatic carcinoma in formalin-fixed, paraffin-embedded tissues. We performed a detailed analysis of P504S protein expression in a large series of prostate and bladder specimens with special emphasis on staining in specific morphologic patterns of prostatic adenocarcinoma, posthormonal and radiation therapy cases, and invasive urothelial carcinoma. A total of 366 prostate needle core biopsies from 124 patients with prostate cancer, 10 biopsies from 2 patients without prostate cancer, 28 prostatectomy specimens (16 with specific morphologic patterns, 7 posthormonal therapy and 5 postradiation therapy specimens), 5 bladder specimens with invasive urothelial carcinoma, and a single transurethral resection specimen from a patient with hormonally treated prostate cancer and invasive urothelial carcinoma were stained with P504S monoclonal antibody at a 1:250 dilution using standard heat-induced epitope retrieval and avidin-biotin technique. Extent (0, no staining; 1+, 1-10% staining; 2+, 11-50% staining; 3+, > or =51% staining) and location (luminal, subluminal, and diffuse cytoplasmic) of immunoreactivity in carcinoma and benign tissues were recorded. A total of 153 of 186 biopsies (82%) with prostatic adenocarcinoma stained for P504S. Pseudohyperplastic, atrophic, ductal, and mucinous prostatic carcinomas stained similarly, as did cases treated with hormone or radiotherapy. In 81 of 377 (21%) foci of benign prostatic tissue there was staining that was almost always focal, faint, and noncircumferential. Seminal vesicles did not stain for P504S. Five of six (83%) specimens with invasive urothelial carcinoma had 2+ staining and one case had focal staining. We conclude that immunohistochemistry for P504S has potential utility in the diagnosis of prostate cancer, including those treated by hormones and radiation. Circumferential luminal to subluminal and diffuse cytoplasmic staining is the most specific staining pattern for prostatic carcinoma and is almost never associated with benign prostatic tissue. However, a negative P504S immunostain does not automatically rule out prostate cancer, as 18% of cases were negative. Additionally, occasional benign glands, high-grade prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, and urothelial carcinoma may express P504S. Therefore, we think that P504S is best used only in conjunction with strict light microscopic correlation and preferably with high molecular weight cytokeratin immunostaining.

Screening positive urine pregnancy tests for sexually transmitted diseases expedites the treatment of infected adolescent gravidas.

OBJECTIVE: To test the utility of screening the urine samples used to diagnose pregnancies at urban teen clinics for Chlamydia trachomatis and Neisseria gonorrhoeae by polymerase chain reaction (PCR). We hypothesized that urine screening would increase the proportion of teenagers treated for these two sexually transmitted diseases (STDs) before they initiated pregnancy-related care. DESIGN: A randomly selected subset of the urine samples used to diagnose 212 teen pregnancies were tested for C. trachomatis and N. gonorrhoeae by PCR. Endocervical testing was at the providers' discretion. Bivariate analyses were used to compare the teenagers randomized to the urine screening group (n = 102) and the non-screening group (n = 110). RESULTS: Of the 102 urine PCR tests, 14 (13.7%) were positive. Endocervical swabs were obtained in 31 (14.6%) of the 212 teenagers and five (16.1%) were positive. Since pelvic examinations were performed so infrequently, the net endocervical swab detection rate was significantly lower than the urine-based detection rate (1.8% compared to 13.7%; p = 0.001). Only one infected teenager was untreated when she initiated pregnancy-related care. Thus, the treatment rate was more than six times higher when urine samples were screened (12.7% compared to 1.8%; p = 0.003). CONCLUSIONS: Screening the urine samples used to diagnose teen pregnancies for two common STDs is a simple, non-invasive procedure that is acceptable to providers and patients, and significantly increases the number of teenagers who are treated for genital infection before they initiate pregnancy-related care.

To be rather than not to be--that is the problem with the questions we ask adolescents about their childbearing intentions.

OBJECTIVE: To demonstrate that rephrasing the questions used to assess childbearing intentions to quantify the strength of the intent to remain nonpregnant, rather than the strength of the intent to become pregnant, would make teenagers' responses more useful to health care providers, family planning counselors, and health policy makers. METHODS: Examples from the teen pregnancy prevention literature are used to support the recommendations for change. RESULTS: Teenagers rarely plan their pregnancies. However, because those who are having sexual intercourse must actively try not to become pregnant or they will likely conceive, teenagers often become pregnant because they lack a firm commitment not to do so. Thus, to accurately profile the antecedents of adolescent pregnancy, (1) the questions used to assess childbearing intentions must be rephrased so that teenagers who intend to remain nonpregnant can be distinguished from those who do not and (2) separate differential diagnoses must be developed for inconsistent contraceptive use within these 2 groups of teenagers who are at risk for unintended pregnancy. CONCLUSION: Asking sexually active teenagers about the strength of their intent to remain nonpregnant will make the results of office interviews and national surveys more useful because the responses such questions elicit will enable health care providers and policy makers to target common, modifiable antecedents of inconsistent contraceptive use for interventions.

Anticonvulsants-induced chorea: a role for pharmacodynamic drug interaction?

Chorea is a rare side effect of anticonvulsants. We describe three patients who developed chorea secondary to anticonvulsant combination use. A mechanism to explain this finding is proposed. After identification of an index case with anticonvulsant-induced chorea, we reviewed the electronic data base records for all patients with seizures followed in the epilepsy clinics at our university-based hospital for cases of dyskinesia associated with anticonvulsants. Two additional patients, one adult and one pediatric patient were identified. Three patients developed chorea while receiving combination anticonvulsants. Two patients had transient chorea that resolved with withdrawal of one of the drugs. All three patients were using phenytoin and lamotrigine in combination when the chorea started, chorea improved with tapering one of the medications. Polytherapy with certain anticonvulsants may predispose patients to drug-induced chorea. A particular increased risk was seen with combinations that have phenytoin and lamotrigine. This could be due to an additive or a synergistic effect on central dopaminergic pathways.

Continuous-wave and passively Q-switched cladding-pumped planar waveguide lasers.

Greater than 12 W of average output power has been generated from a diode-pumped Yb:YAG cladding-pumped planar waveguide laser. The laser radiation developed is linearly polarized and diffraction limited in the guiding dimension. A slope efficiency of 0.5 W/W with a peak optical-optical conversion efficiency of 0.31 W/W is achieved. In a related structure, greater than 8 W of Q -switched average output power has been generated from a Nd:YAG cladding-pumped planar waveguide laser by incorporation of a Cr(4+): YAG passive Q switch monolithically into the waveguide structure. Pulse widths of 3 ns and pulse-repetition frequencies as high as 80 kHz have been demonstrated. A slope efficiency of 0.28 W/W with a peak optical-optical conversion efficiency of 0.21 W/W is achieved.