Syosset Hospital

Ninety-seven percent of drug-indication pairs that are tested in clinical trials in oncology never advance to receive U.S. Food and Drug Administration approval. While lack of efficacy and dose-limiting toxicities are the most common causes of trial failure, the reason(s) why so many new drugs encounter these problems is not well understood. Using CRISPR-Cas9 mutagenesis, we investigated a set of cancer drugs and drug targets in various stages of clinical testing. We show that-contrary to previous reports obtained predominantly with RNA interference and small-molecule inhibitors-the proteins ostensibly targeted by these drugs are nonessential for cancer cell proliferation. Moreover, the efficacy of each drug that we tested was unaffected by the loss of its putative target, indicating that these compounds kill cells via off-target effects. By applying a genetic target-deconvolution strategy, we found that the mischaracterized anticancer agent OTS964 is actually a potent inhibitor of the cyclin-dependent kinase CDK11 and that multiple cancer types are addicted to CDK11 expression. We suggest that stringent genetic validation of the mechanism of action of cancer drugs in the preclinical setting may decrease the number of therapies tested in human patients that fail to provide any clinical benefit.

Agroecology is in fashion, and now constitutes a territory in dispute between social movements and institutionality. This new conjuncture offers a constellation of opportunities that social movements can avail themselves of to promote changes in the food system. Yet there is an enormous risk that agroecology will be co-opted, institutionalized, colonized and stripped of its political content. In this paper, we analyze this quandary in terms of political ecology: will agroecology end up as merely offering a few more tools for the toolbox of industrial agriculture, to fine tune an agribusiness system that is being restructured in the midst of a civilizational crisis or, alternatively, will it be strengthened as a politically mobilizing option for building alternatives to development? We interpret the contemporary dispute over agroecology through the lenses of contested material and immaterial territories, political ecology, and the first and second contradictions of capital.

The Caprini risk assessment model (RAM) has been validated in over 250 000 patients in more than 100 clinical trials worldwide. Ultimately, appropriate treatment options are dependent on precise completion of the Caprini RAM. As the numerical score increases, the clinical venous thromboembolism rate rises exponentially in every patient group where it has been properly tested. The 2013 Caprini RAM was completed by specially trained medical students via review of the presurgical assessment history, medical clearances, and medical consults. The Caprini RAM was completed for every participant both preoperatively and predischarge to ensure that any changes in the patient's postoperative course were captured by the tool. This process led to the development of completion guidelines to ensure consistency and accuracy of scoring. The 2013 Caprini scoring system provides a consistent, thorough, and efficacious method for risk stratification and selection of prophylaxis for the prevention of venous thrombosis.

Ocular lesions have been experimentally produced in rabbit by a pulsed optical maser (laser). The high-energy density delivered in a single 0.5 msec pulse was sufficient to cause instantaneous thermal injury to the pigmented retina and iris of the brown rabbit. Ophthalmoscopically, the retinal lesions resembled flash burns from an atomic fireball.

ABSTRACT: Hydrograph analysis of six streams on the south shore of Long Island indicates that eastward urbanization during the last three decades has significantly reduced base flow to streams. Before urbanization, roughly 95 percent of total annual stream flow on Long Island was base flow. In urbanized southwestern Nassau County, storm water sewerage, increased impervious surface area, and sanitary sewerage have reduced base flow to 20 percent of total stream flow. In an adjacent urbanized but unsewered area in southeastern Nassau County, base flow has decreased to 84 percent of total annual stream flow. In contrast, base flow in two streams in rural areas has remained virtually constant, averaging roughly 95 percent of total annual flow throughout the 1955‐70 study period. Double‐mass curve analysis of base flow as a percentage of total annual stream flow indicates that (1) changes in stream flow characteristics began in the early 1960's in the sewered area and in the late 1960's in the later urbanized, unsewered area, and (2) a new equilibrium has been established between the streams in the sewered area and the new hydrologic characteristics of their urbanized drainage basins.

A continuously operating 7.18-μ laser oscillator has been built using optically pumped cesium vapor as the amplifying medium. A power of 50 μw is coupled out of the confocal resonator by means of a 45° BaF2 pickoff window. The measured intensity distribution is in good agreement with that derived from the Boyd-Gordon expression for the lowest-order mode.

Received 11 September 1961DOI:https://doi.org/10.1103/PhysRevLett.7.415©1961 American Physical Society

Appropriate chemoprophylaxis choice following arthroplasty requires accurate patient risk assessment. We compared the results of our prospective department protocol to the Caprini risk assessment model (RAM) retrospectively in this study group. Our goal was to determine whether the department protocol or the Caprini score would identify venous thromboembolism (VTE) events after total joint replacement. A secondary purpose was to validate the 2013 Caprini RAM in joint arthroplasty and determine whether patients with VTE would be accurately identified using the Caprini score. A total of 1078 patients met inclusion criteria. A Caprini score of 10 or greater is considered high risk and a score of 9 or less is considered low risk. The 2013 version of the Caprini RAM retrospectively stratified 7 of the 8 VTE events correctly, while only 1 VTE was identified with the prospective department protocol. This tool provided a consistent, accurate, and efficacious method for risk stratification and selection of chemoprophylaxis.

It is shown, for the case of forced simple harmonic heave, that if the damping parameter is known for all frequencies then the virtual mass parameter (minus its value at infinite frequency) is readily determined for all frequencies, and vice versa, b

Morphological changes at the cell level have been produced experimentally by a pulsed ruby laser (optical maser). A pulse duration of approximately 500 microseconds caused discrete damage to structures in the cell without irreversible damage to the surrounding area.

The nonlinear properties of a power-saturated resonant medium are used to obtain amplification of millimeter-wave radiation. Experiments demonstrating this effect are performed with the 3.5-mm rotational resonance of hydrogen cyanide (H${\mathrm{C}}^{12}$${\mathrm{N}}^{15}$) gas. An incoming radiation spectrum consisting of a strong saturating component at 3.5 mm and weak sidebands is transmitted through a gas-filled, $\frac{3}{4}$-in.-diam, 20-ft circular waveguide operated in the $T{E}_{01}$ mode. Under certain conditions power can be transferred from the strong saturating component to the weak sidebands. A sideband gain with a maximum value of 1.5 dB is measured when the sidebands are phased for amplitude modulation and the saturating component input power is 4.8 mW. The bandwidth for this type of amplification is equal to the power-broadened linewidth. Sidebands phased for frequency modulation are always attenuated. The experimental results are in agreement with computations based on the solution of the quantum-mechanical Boltzmann equation. These computations indicate that a single sideband can also be amplified.

The Fabry-Perot interferometer has been suggested for use as a high-mode LASER (light amplification by stimulated emission of radiation) resonator. The oscillation condition for a Fabry-Perot LASER is derived from an integral equation for the angular spectrum of the field. The kernel of the integral equation involves the scattering matrices of the end mirrors. This integral equation leads to a stationary expression. The use of physically reasonable trial spectra allows one to estimate the effect of ``walkoff,'' diffraction, reflector curvature, and reflector tilt in terms of an ``effective'' reflection coefficient for the infinite-aperture Fabry-Perot. Taking into account the effect of ``walkoff,'' an approximate necessary and sufficient condition for oscillation normal to the reflectors is derived.

Online Q & A services are information sources where people identify their information need, formulate the need in natural language, and interact with one another to satisfy their needs. Even though in recent years online Q & A has considerably grown in popularity and impacted information‐seeking behaviors, we still lack knowledge about what motivates people to ask a question in online Q & A environments. Yahoo! Answers and WikiAnswers were selected as the test beds in the study, and a sequential mixed method employing an Internet‐based survey, a diary method, and interviews was used to investigate user motivations for asking a question in online Q & A services. Cognitive needs were found as the most significant motivation, driving people to ask a question. Yet, it was found that other motivational factors (e.g., tension free needs) also played an important role in user motivations for asking a question, depending on asker's contexts and situations. Understanding motivations for asking a question could provide a general framework of conceptualizing different contexts and situations of information needs in online Q & A . The findings have several implications not only for developing better question‐answering processes in online Q & A environments, but also for gaining insights into the broader understanding of online information‐seeking behaviors.

At the current time, there is increasing recognition of the need for services for children on the autistic spectrum. While this remains critical, it is also important for professionals to recognize the reciprocal relationship between family functioning and the outcome of services for children. An understanding of the range of stressors on the family system, family values, culture, and priorities can help shape intervention goals. This article reviews the impact of this diagnosis on the entire family system and the utilization of the family perspective to address some of the complex needs of both children and their families.

Given the Lyapunov matrix equation <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">A'Q + QA = -P</tex> a fundamental inequality which is satisfied by the extremal eigenvalues of the matrices <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</tex> and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P</tex> , provided <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">A</tex> is a stability matrix, is established. This result, besides being interesting from a theoretical standpoint, is extremely useful in the determination of suboptimal controllers for the minimum time problem [1].

The optical mode structure of a Fabry—Perot interferometer-resonator composed of two infinite strip mirrors is investigated from the point of view of the general theory of nonspectral resonances. It is shown that the classical description of this configuration is inadequate to describe its response to highly monochromatic laser radiation and must be supplemented by a discussion of the transverse resonance behavior. This introduces a fine structure to the classical Fabry—Perot rings and implies a discrete resonance behavior for the Fabry—Perot interferometer. In analogy to the characterization of quantum-mechanical virtual levels by wavefunctions and complex energies it is convenient to characterize the discrete resonances of a Fabry—Perot by mode functions and complex resonant frequencies. On the basis of a reformulation and asymptotic expansion of a previously given stationary expression, it is shown that in the high-frequency limit, the open sides of the structure can be replaced by an effective impedance boundary condition. The solution of an elementary resonance problem then yields analytic approximations for the mode shapes, characteristic oscillation frequencies, and modal lifetimes. In the common domain of validity these results are in excellent agreement with previous numerical work on this problem.

OBJECTIVE: Estimation of the specific thresholds of the Caprini risk score (CRS) that are associated with the increased incidence of venous thromboembolism (VTE) across different specialties, including identifying the highest level of risk. BACKGROUND: Accurate risk assessment remains an important but often challenging aspect of VTE prophylaxis. One well-established risk assessment model is CRS, which has been validated in thousands of patients from many different medical and surgical specialties. METHODS: A search of MEDLINE and the Cochrane Library was performed in March 2022. Manuscripts that reported on (1) patients admitted to medical or surgical departments and (2) had their VTE risk assessed by CRS and (3) reported on the correlation between the score and VTE incidence, were included in the analysis. RESULTS: A total of 4562 references were identified, and the full text of 202 papers was assessed for eligibility. The correlation between CRS and VTE incidence was reported in 68 studies that enrolled 4,207,895 patients. In all specialties, a significant increase in VTE incidence was observed in patients with a CRS of ≥5. In most specialties thresholds of ≥7, ≥9, and ≥11 to 12 were associated with dramatically increased incidences of VTE. In COVID-19, cancer, trauma, vascular, general, head and neck, and thoracic surgery patients with ≥9 and ≥11 to 12 scores the VTE incidence was extremely high (ranging from 13% to 47%). CONCLUSION: The Caprini score is being used increasingly to predict VTE in many medical and surgical specialties. In most cases, the VTE risk for individual patients increases dramatically at a threshold CRS of 7 to 11.

Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hypodopaminergia. Evaluation of pain clinic patients with the Genetic Addiction Risk Score (GARS) test and the Addiction Severity Index (ASI- Media Version V) revealed that GARS scores equal to or greater than 4 and 7 alleles significantly predicted drug and alcohol severity, respectively. We utilized RT-PCR for SNP genotyping and multiplex PCR/capillary electrophoresis for fragment analysis of the role of eleven alleles in a ten-reward gene panel, reflecting the activity of brain reward circuitry in 121 chronic opioid users. The study consisted of 55 males and 66 females averaging ages 54 and 53 years of age, respectively. The patients included Caucasians, African Americans, Hispanics, and Asians. Inclusion criteria mandated that the Morphine Milligram Equivalent (MME) was 30-600 mg/day (males) and 20 to 180 mg/day (females) for treatment of chronic pain over 12 months. Ninety-six percent carried four or more risk alleles, and 73% carried seven or more risk alleles, suggesting a high predictive risk for opioid and alcohol dependence, respectively. These data indicate that chronic, legally prescribed opioid users attending a pain clinic possess high genetic risk for drug and alcohol addiction. Early identification of genetic risk, using the GARS test upon entry to treatment, may prevent iatrogenic induced opioid dependence.

Abstract The accretion-powered X-ray pulsar GX 301−2 was observed with the balloon-borne X-Calibur hard X-ray polarimeter during late 2018 December, with contiguous observations by the Neutron star Interior Composition Explorer Mission ( NICER ) X-ray telescope, the Swift X-ray Telescope and Burst Alert Telescope, and the Fermi Gamma-ray Burst Monitor spanning several months. The observations detected the pulsar in a rare apastron flaring state coinciding with a significant spin up of the pulsar discovered with the Fermi Gamma-ray Burst Monitor. The X-Calibur , NICER , and Swift observations reveal a pulse profile strongly dominated by one main peak, and the NICER and Swift data show strong variation of the profile from pulse to pulse. The X-Calibur observations constrain for the first time the linear polarization of the 15–35 keV emission from a highly magnetized accreting neutron star, indicating a polarization degree of % (90% confidence limit) averaged over all pulse phases. We discuss the spin up and the X-ray spectral and polarimetric results in the context of theoretical predictions. We conclude with a discussion of the scientific potential of future observations of highly magnetized neutron stars with the more sensitive follow-up mission XL-Calibur .

A method of geometrically determining Position Dilution of Precision (PDOP) is given. The method gives an insight which is lacking in the purely mathematical determination. The method applies to 3-dimensional GPS fixes. With slight modification it can be applied to 2-dimensional GPS fixes, to 2-dimensional hyperbolic fixes, or to 2-dimensional range-range fixes. Practical examples are given, and the results are shown to agree with the purely mathematical determination.