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Quantitatively determining in vivo achievable drug concentrations in targeted organs of animal models and subsequent target engagement confirmation is a challenge to drug discovery and translation due to lack of bioassay technologies that can discriminate drug binding with different mechanisms. We have developed a multiplexed and high-throughput method to quantify drug distribution in tissues by integrating high content screening (HCS) with U-Net based deep learning (DL) image analysis models. This technology combination allowed direct visualization and quantification of biologics drug binding in targeted tissues with cellular resolution, thus enabling biologists to objectively determine drug binding kinetics.

Purpose To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

We develop a framework that allows a description of measurements in Hilbert spaces that are smaller than their natural representation. This description, which we call a "squashing model", consists of a squashing map that maps the input states of the measurement from the original Hilbert space to the smaller one, followed by a targeted prescribed measurement on the smaller Hilbert space. This framework has applications in quantum key distribution, but also in other cryptographic tasks, as it greatly simplifies the theoretical analysis under adversarial conditions., Comment: 24 pages main text, 12 figures, 4 pages appendix, 1 figure

Quantum key distribution protocols typically make use of a one-way quantum channel to distribute a shared secret string to two distant users. However, protocols exploiting a two-way quantum channel have been proposed as an alternative route to the same goal, with the potential advantage of outperforming one-way protocols. Here we provide a strategy to prove security for two-way quantum key distribution protocols against the most general quantum attack possible by an eavesdropper. We utilize an entropic uncertainty relation, and only a few assumptions need to be made about the devices used in the protocol. We also show that a two-way protocol can outperform comparable one-way protocols., Physical Review A, 88 (6), ISSN:1094-1622, ISSN:0556-2791, ISSN:1050-2947

The effective analysis and interpretation of high-content screening (HCS) data requires joining results to information on experimental treatments and controls, normalizing data, and selecting hits or fitting concentration-response curves. HCS data have unique requirements that are not supported by traditional high-throughput screening databases, including the ability to designate separate positive and negative controls for different measurements in multiplexed assays; the ability to capture information on the cell lines, fluorescent reagents, and treatments in each assay; the ability to store and use individual-cell and image data; and the ability to support HCS readers and software from multiple vendors along with third-party image analysis tools. To address these requirements, the authors developed an enterprise system for the storage and processing of HCS images and results. This system, HCS Road, supports target identification, lead discovery, lead evaluation, and lead profiling activities. A dedicated client supports experimental design, data review, and core analyses and displays images together with results for assay development, hit assessment, and troubleshooting. Data can be exported to third-party applications for further analysis and exploration. HCS Road provides a single source for high-content results across the organization, regardless of the group or instrument that produced them.

Quantum Key Distribution offers the promise of secure communication at unprecedented security level. Secure systems can be implemented by standard optical communication components - if done right. We report on the divide of right and wrong.

Preserving the integrity of the compound collection and providing high-quality materials for drug discovery in an efficient and cost-effective manner are 2 major challenges faced by compound management (CM) at Bristol-Myers Squibb (BMS). The demands on CM include delivering hundreds of thousands of compounds a year to a variety of operations. These operations range from single-compound requests to hit identification support and just-in-time assay plate provision for lead optimization. Support needs for these processes consist of the ability to rapidly provide compounds as solids or solutions in a variety of formats, establishing proper long- and short-term storage conditions and creating appropriate methods for handling concentrated, potent compounds for delivery to sensitive biological assays. A series of experiments evaluating the effects of processing compounds with volatile solvents, storage conditions that can induce freeze/thaw cycles, and the delivery of compounds were performed. This article presents the results of these experiments and how they affect compound integrity and the accuracy of compound management processes.

A terahertz frequency domain spectrometer is implemented using two ErAs:GaAs photomixers in a highly compact configuration, utilizing all solid-state components and no moving parts. Digital signal processing electronics provide precise frequency control and yield ~200 MHz accuracy of the THz signal frequency. Continuous frequency sweeping is demonstrated with better than 1 GHz resolution from 200 GHz to 1.85 THz. The coherent detection sensitivity is shown to be in good agreement with previous theoretical predictions and yields a signal-to-noise ratio of 80 dB*Hz at 200 GHz and 60 dB*Hz at 1 THz through a path length in air of one foot.

This article is a practical review of the current psychopharmacological agents used in the treatment of child and adolescent psychiatric disorders. Psychostimulants such as methylphenidate, dexamphetamine and pemoline are effective in the control of symptoms associated with attention deficit hyperactivity disorder. The controlled release preparations and the adjunctive use of clonidine are helpful to extend stimulant effects and control adverse effects. Tricyclic antidepressants are helpful in individual cases of child and adolescent depression, but adverse effects may limit their use. Clomipramine has been found to be effective for childhood obsessive-compulsive disorder. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) appear to be safer for depression and are also useful in obsessive-compulsive disorder. Buspirone is effective for the treatment of anxiety disorders in children. Newer atypical antipsychotics such as risperidone may have less limiting adverse effects than older antipsychotics in the treatment of psychosis and severe behaviour disorders, but the physician must be vigilant for the emergence of tardive dyskinesia. Drug treatment in children and adolescents must take into account the child's environmental influences and be part of an overall treatment plan where individual, familial and cultural issues are addressed.

A retrospective study of 69 cases of infective endocarditis in 68 children (group I: 1971-1981; 34 children; group II: 1982-1992; 34 children) disclosed the following features: a moderate increase in the global incidence of infective endocarditis (0.5% of children hospitalized in paediatric cardiology units) and of its incidence in the very young (proportion of children less than 1 year of age: 9% in group I and 17% in group II); no rheumatic heart disease amongst predisposing heart diseases in children living in France; a major causal role of congenital heart diseases (72%), with an increasing incidence of previous operation (group I:42%; group II:56%); an increase in associated complex congenital heart diseases (group I: 11%; group II: 20%); no change in related mitral valve prolapse (5% in both groups); positive blood cultures in 76% of cases, with similar rates of Staphylococci (group I: 27%; group II: 30%) and of unusual microorganisms (15% in both groups); a major diagnostic role for echocardiography (vegetations in group II: 64%). Complications occurred in 75% of cases in both groups (pulmonary or systemic emboli, mycotic aneurysms, valvar regurgitation), leading to heart failure in 29% of group I patients and in 32% of group II patients. Mortality has decreased, from 12% in group I to 3% in group II, as a result of more frequent cardiovascular surgery (group I: 11 cases; group II: 15 cases), problems due to restrictive prostheses, and severe consequences: only 27% of group II children were cured without deterioration of their cardiac condition. These data confirm that the natural history of infective endocarditis has changed over the last two decades

An electrophysiologic study was performed in the first month of life in a patient with the congenital long QT syndrome and spontaneous episodes of 2/1 atrioventricular block. The block could be reproduced by incremental atrial pacing, and its infrahisian location was associated with a prolongation of the refractoriness in the ventricular muscle itself. Surprisingly, intravenous propranolol aggravated this phenomenon by further prolonging the QT interval. Sudden death occurred shortly thereafter during Holter monitoring and was due to a sudden resumption of normal AV conduction after an episode of 2:1 block, immediately followed by ventricular fibrillation.

The aim of the present study was to assess the validity of different self-reported questions for measuring exercise behavior of 551 employees. Values of maximum oxygen intake, body mass index, muscular endurance, and a fitness profile, based on the individual results obtained from each of the three physiologic parameters, were used as validity criteria for the self-reported measures. The influence of fitness profile on the measures of exercise habits indicated that the fit employees reported a more active pattern of exercise behavior, participated in more strenuous physical activity, and expended a greater amount of energy in a typical week than the unfit employees. There was no gain obtained in explaining fitness categorization with a more elaborate method compared with a simple question in measuring exercise behavior. The results of the present study show that the suggested simple method (one question) for assessing exercise behavior of employees is valid and can be useful for nurses and company physicians when evaluating the baseline behavior of a group of employees to assess the impact of exercise promotion programs at the work site.

Malignant tumors in the head and neck region are rare in patients under the age of 30 years. The survival rate in our group compared favorably with the rate for adults with similar tumors and supports the administration of aggressive treatment. Radiation therapy in the formative years can arrest skeletal growth and cause tissue atrophy which produces facial asymmetry, but it does give in balance a better functional result and less mutilation than does radical surgery. The risk of development of a second malignant tumor with the administration of modern treatment appears to be minimal. There is an urgent need for better documentation of etiologic factors.

In a series of 42 bladder cancers treated with combined transurethral resection and external supervoltage Co/sup 60/ irradiation, 37% survived 3 yr or longer irrespective of stage and grade. The total calculated tumor dose of the bladder varied from just under 6000 r in 10 patients to 6000 r in 30 patients, and to over 6000 r in 2 additional patients. The overall time of treatment was 6 weeks. The delivery of a cancerocidal dose to the bladder was accompanied by increased urinary and bowel symptoms. Of 42 patients, 32 had pre-existing hematuria, and in 25 of the 32 this was the sole symptom. Thirteen other patients had multiple symptoms of urgency, frequency, dysuria, and nocturia. In 7 patients there was no aggravation of preexisting symptoms; in 31, symptoms were increased. In 16 of the 31 patients with aggravated symptoms, diarrhea was associated and in 9 of the 16 patients, diarrhea preceded urinary symptoms by a 1000 to 3000-r tumor dose. The tumor dose at which urinary symptoms first appeared was as follows: 5 cases, under 2000 r; 11 cases, 2000 to 4000 r; 12 cases, 4000 to 6000 r. Following the completion of irradiation 23 patients had persistent symptoms;more » in 10, urinary symptoms were associated with cystoscopically verified radiation cystitis which continued 6 to 12 months beyond the course of cobalt therapy. (H.H.D.)« less

The method of administration of radioactive isotopes in the treatment of pleural effusions and ascites associated with cancer will vary according to the therapeutic technic (1–5). A procedure with a suitable apparatus that utilizes an economical and sterile disposable package is described in this paper. The apparatus, shown in Figure 1, consists of: polyethylene or nylon tubing with an interior diameter of 0.70 inch; 4 stainless steel clamps; 3 No. 15 hypodermic needles of 3 1/2 inches length; 1 ampule of 5.0 c.c. Evans blue; 500 c.c. isotonic saline solution; 1 Cly-Q-Pak2; 2 Donopak 242; one Y connector.2 All the equipment is supplied sterile or can be sterilized. The radioactive isotope, whether colloidal chromic phosphate (P32) or colloidal gold (Au198), can be obtained in the exact amount prescribed. The entire apparatus is assembled within a few minutes under sterile conditions (Fig. 2). Before the hypodermic needles are inserted into the radioactive isotope vial, the air is removed from the tubing b...

Association between bacterial endocarditis (BE) and vertebral osteomyelitis (VO) has infrequently been noted. In a retrospective analysis of BE (280 cases) and VO (150 cases) 14 cases were found to have this association. There were 12 males and 2 females, ages ranging from 39 to 72 years, mean age 56.6. Blood cultures were positive for Streptococcus viridans (6 cases). Str. faecalis (4 cases), staphylococcus (2 cases), Gram negative bacteria (1 case). Organism was not isolated in one case. Fever and severe back pain antedate the diagnosis of VO 3.5 and 2.5 months. X rays films of the spine and bone scans (4 cases) revealed lumbar (6 cases) or cervical (4 cases), or dorsal (3 cases) or combined cervical and dorsal (1 case) locations. History of murmur (4 cases) and development of mitral (8 cases) or aortic (4 cases) or combined mitral and aortic (2 cases) insufficiencies were consistent with concomitant BE. Echocardiogram revealed vegetations in 6 out of 9 cases. Patients received antibiotic therapy for 3.5 months. Ten patients were cured with antibiotics only, 4 required valve replacement. One died. Thus age, sex, history of heart disease, valvular involvement, duration of symptoms prior to admission and bacteriological pictures are the same in BE with VO as in BE without VO. Survival rates are also the same if early recognition of BE and VO with prompt and prolonged antibiotic therapy may prevent severe haemodynamic or vertebral problems.