Chronic Microangiopathy Due to DCR-MYC, a Myc-Targeted Short Interfering RNA.

Thrombotic microangiopathy (TMA) is an emerging complication of oncologic therapy. Cancer-related causes of renal endothelial cell damage include cytotoxic chemotherapies, radiation given for myeloablation, and direct involvement of renal vasculature by tumor cells. Another class of therapeutic agents that has been implicated in TMA is the vascular endothelial growth factor (VEGF) pathway inhibitors, including the anti-VEGF monoclonal antibody bevacizumab and the VEGF receptor tyrosine kinase inhibitor sunitinib. These TMAs have been termed type II cancer drug-induced TMA and are distinguished from those associated with some cytotoxic chemotherapies (ie, type I) in that they are not dose dependent and patients are more likely to demonstrate some recovery of kidney function. Determination of the cause of TMA in oncologic patients often presents a significant challenge because patients frequently receive multiple chemotherapeutic agents simultaneously and clinicopathologic features often demonstrate substantial overlap, regardless of cause. We present a case of TMA with predominantly chronic features in a 70-year-old patient being treated for adenoid cystic carcinoma of the breast with a single agent, a short interfering RNA targeted against Myc (DCR-MYC).

Are one-stop centres an appropriate model to deliver services to sexually abused children in urban Malawi?

BACKGROUND: The Republic of Malawi is creating a country-wide system of 28 One-Stop Centres (known as 'Chikwanekwanes' - 'everything under one roof') to provide medical, legal and psychosocial services for survivors of child maltreatment and adult intimate partner violence. No formal evaluation of the utility of such services has ever been undertaken. This study focused on the experiences of the families served at the country's first Chikwanekwane in the large, urban city of Blantyre. METHODS: One hundred seven families were surveyed in their home three months after their initial evaluation for sexual abuse at the Blantyre One Stop Centre, and 25 families received a longer interview. The survey was designed to inquire what types of initial evaluation and follow-up services the children received from the medical, legal and social welfare services. RESULTS: All 107 received an initial medical exam and HIV testing, and 83% received a follow-up HIV test by 3 months; 80.2% were seen by a social welfare worker on the initial visit, and 29% had a home visit by 3 months; 84% were seen by a therapist at the initial visit, and 12% returned for further treatment; 95.3% had an initial police report and 27.1% ended in a criminal conviction for child sexual abuse. Most of the families were satisfied with the service they received, but a quarter of the families were not satisfied with the law enforcement response, and 2% were not happy with the medical assessment. CONCLUSIONS: Although a perception of corruption or negligence by police may discourage use of service, we believe that the One-Stop model is an appropriate means to deliver high quality care to survivors of abuse in Malawi.

Educating physicians internationally in the diagnosis of child sexual abuse: evaluation of a brief educational intervention in Malawi.

We designed this pilot study to assess physician knowledge and comfort evaluating child sexual abuse in Malawi and to evaluate the feasibility of a brief educational intervention to improve physician knowledge. A survey was administered to 21 physicians before receiving training on child sexual abuse. The survey was administered again, 3 days later, to assess improvement. Prior to the training, 48% correctly identified the hymen in a photograph, and 24% correctly interpreted the photograph as normal. Of the 11 physicians available for the posttest 3 days later, significant improvement was found in their ability to correctly identify the hymen (6 of 11 pretraining and all 11 posttraining, p = 0.011) and to interpret the photograph correctly (1 of 11 correct pretraining, 9 of 11 posttraining, p = 0.001). This study demonstrates the feasibility of designing trainings on child sexual abuse in a low-income country.

First-in-clinical application of a time-gated diffuse correlation spectroscopy system at 1064†nm using superconducting nanowire single photon detectors in a neuro intensive care unit.

Recently proposed time-gated diffuse correlation spectroscopy (TG-DCS) has significant advantages compared to conventional continuous wave (CW)-DCS, but it is still in an early stage and clinical capability has yet to be established. The main challenge for TG-DCS is the lower signal-to-noise ratio (SNR) when gating for the deeper traveling late photons. Longer wavelengths, such as 1064 nm have a smaller effective attenuation coefficient and a higher power threshold in humans, which significantly increases the SNR. Here, we demonstrate the clinical utility of TG-DCS at 1064 nm in a case study on a patient with severe traumatic brain injury admitted to the neuro-intensive care unit (neuroICU). We showed a significant correlation between TG-DCS early (ρ = 0.67) and late (ρ = 0.76) gated against invasive thermal diffusion flowmetry. We also analyzed TG-DCS at high temporal resolution (50 Hz) to elucidate pulsatile flow data. Overall, this study demonstrates the first clinical translation capability of the TG-DCS system at 1064 nm using a superconducting nanowire single-photon detector.

Compact cryogenic self-aligning fiber-to-detector coupling with losses below one percent.

We present a compact packaging technique for coupling light from a single-mode telecommunication fiber to cryogenic single-photon sensitive devices. Our single-photon detectors are superconducting transition-edge sensors (TESs) with a collection area only a factor of a few larger than the area of the fiber core which presents significant challenges to low-loss fiber-to-detector coupling. The coupling method presented here has low loss, cryogenic compatibility, easy and reproducible assembly and low component cost. The system efficiency of the packaged single-photon counting detectors is verified by the "triplet method" of power-source calibration along with the "multiple attenuator" method that produces a calibrated single-photon flux. These calibration techniques, when used in combination with through-wafer imaging and fiber back-reflection measurements, give us confidence that we have achieved coupling losses below 1% for all devices packaged according to the self-alignment method presented in this paper.

Noninvasive Optical Monitoring of Cerebral Blood Flow and EEG Spectral Responses after Severe Traumatic Brain Injury: A Case Report.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. We utilized the diffuse correlation spectroscopy method for assessing cerebral blood flow at the neuro-ICU in a patient with traumatic brain injury. The present case demonstrates the feasibility of continuous recording of noninvasive cerebral blood flow transients that correlated well with the gold-standard invasive measurements and with the frequency content changes in the EEG data.

Featured counter trafficking program: The law enforcement first responder protocol.

This invited article is one of several comprising part of a special issue of Child Abuse and Neglect focused on child trafficking and health. The purpose of each invited article is to describe a specific program serving trafficking children. Featuring these programs is intended to raise awareness of innovative counter-trafficking strategies emerging worldwide and facilitate collaboration on program development and outcomes research. This article describes the Law Enforcement First Responder Protocol, which trained law enforcement to recognize youth engaged in sex work as survivors of commercial sexual exploitation, rather than as "prostitutes", and to connect these survivors immediately with social services, advocates, timely medical care and ongoing follow-up.

Ethical Testimony in Cases of Suspected Child Maltreatment: The Ray E. Helfer Society Guidelines.

New guidelines for ethical testimony were developed by the Ray E. Helfer Society, the largest medical professional society for physicians working in the field of child maltreatment. Building on the foundation of ethical guidelines set forth by the American Academy of Pediatrics, these new guidelines set detailed standards for testifying in cases of suspected child maltreatment and recommend that hospitals, medical practices, academic institutions, and professional societies hold their members accountable for court testimony related to child maltreatment as with other forms of medical practice and expert testimony.

Counting near-infrared single-photons with 95% efficiency.

Single-photon detectors operating at visible and near-infrared wavelengths with high detection efficiency and low noise are a requirement for many quantum-information applications. Superconducting transition-edge sensors (TESs) are capable of detecting visible and near-infrared light at the single-photon level and are capable of discriminating between one- and two-photon absorption events; however these capabilities place stringent design requirements on the TES heat capacity, thermometry, and optical detection efficiency. We describe the fabrication and evaluation of a fiber-coupled, photon-number-resolving TES detector optimized for absorption at 1550 and 1310 nm wavelengths. The measured system detection efficiency at 1556 nm is 95 % +/- 2 %, which to our knowledge is the highest system detection efficiency reported for a near-infrared single-photon detector.

Single photon source characterization with a superconducting single photon detector.

Superconducting single photon detectors (SSPD) based on nanopatterned niobium nitride wires offer single photon counting at fast rates, low jitter, and low dark counts, from visible wavelengths well into the infrared. We demonstrate the first use of an SSPD, packaged in a commercial cryocooler, for single photon source characterization. The source is an optically pumped, microcavity-coupled InGaAs quantum dot, emitting single photons at 902 nm. The SSPD replaces the second silicon Avalanche Photodiode (APD) in a Hanbury-Brown Twiss interferometer measurement of the source second-order correlation function, g(2)( ?). The detection efficiency of the superconducting detector system is >2 % (coupling losses included). The SSPD system electronics jitter is 170 ps, versus 550 ps for the APD unit, allowing the source spontaneous emission lifetime to be measured with improved resolution.