Achieving the Shot-noise Limit Using Experimental Multi-shot Digital Holography Data

In this paper, we achieve the shot-noise limit using straightforward image-post-processing techniques with experimental multi-shot digital holography data (i.e., off-axis data composed of multiple noise and speckle realizations). First, we quantify the effects of frame subtraction (of the mean reference-only frame and the mean signal-only frame from the digital-hologram frames), which boosts the signal-to-noise ratio (SNR) of the baseline dataset with a gain of 2.4 dB. Next, we quantify the effects of frame averaging, both with and without the frame subtraction. We show that even though the frame averaging boosts the SNR by itself, the frame subtraction and the stability of the digital-hologram fringes are necessary to achieve the shot-noise limit. Overall, we boost the SNR of the baseline dataset with a gain of 8.1 dB, which is the gain needed to achieve the shot-noise limit

'Deadman' and 'Passcode' microbial kill switches for bacterial containment

Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival. The Passcode kill switch uses a similar two-layered transcription design and incorporates hybrid LacI-GalR family transcription factors to provide diverse and complex environmental inputs to control circuit function. These synthetic gene circuits efficiently kill Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism.United States. Defense Threat Reduction Agency (Grant HDTRA1-14-1-0006)Howard Hughes Medical InstituteUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N000141110725)United States. Air Force Office of Scientific Research (Grant FA9550-14-1-0060

Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [18F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [18F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [18F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen's d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence-a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge

Postpneumonectomy syndrome: Surgical management and long-term results

ObjectivePostpneumonectomy syndrome is a rare syndrome of dynamic airway obstruction caused by extreme rotation and shift of the mediastinum after pneumonectomy, resulting in symptomatic central airway compression. We have treated this syndrome by mediastinal repositioning and placement of saline-filled prostheses into the pneumonectomy space. There is a paucity of outcome data for patients treated surgically, with only a single series of 11 patients previously reported. We analyzed our recent experience with treatment of this syndrome and report on the short and long-term outcomes and quality of life assessment of the largest series ever reported of patients treated by mediastinal repositioning.MethodsRecords were reviewed of all patients who underwent mediastinal repositioning for postpneumonectomy syndrome between January of 1992 and June of 2006. Long-term health-related quality of life was assessed by administration of the Saint George's Respiratory Questionnaire.ResultsThere were 18 patients (15 women and 3 men) with a median age of 44 years (range 14–67 years). Thirteen patients had undergone right pneumonectomy, and 5 patients had undergone left pneumonectomy. None of the patients in whom postpneumonectomy syndrome developed after left pneumonectomy had a right-sided aortic arch. Five patients had undergone pneumonectomy in childhood (age < 13 years). The median interval between pneumonectomy and mediastinal repositioning was 7.5 years (range 1.1–54.8 years). The median follow-up was 32 months (range 4–143 months). The operative mortality was 5.6% (1/18). Complications occurred in 5 patients (27.8%): pneumonia in 3 patients and acute respiratory distress syndrome in 2 patients. The median hospitalization was 6 days (range 3–155 days). Some 77% (10/13) of patients reported significant improvement in their breathing and overall state of health after surgery; 15.4% of patients (2/13) were somewhat better, and 7.7% of patients (1/13) had no improvement. No patients' condition was worse after surgery. All patients who reported improvement in their symptoms after surgery remained symptomatically improved at the time of the quality of life assessment. Some 92.3% (12/13) were not at all or only slightly limited in their social activities because of breathing problems, and 84.6% (11/13) were not at all or only slightly limited in their ability to work as a result of their physical health.ConclusionRepositioning of the mediastinum with placement of prostheses for postpneumonectomy syndrome can be performed with low mortality and morbidity. Surgical repositioning provides immediate and lasting symptomatic relief to patients in whom postpneumonectomy syndrome develops

An Upper Mass Limit on a Red Supergiant Progenitor for the Type II-Plateau Supernova SN 2006my

We analyze two pre-supernova (SN) and three post-SN high-resolution images of the site of the Type II-Plateau supernova SN 2006my in an effort to either detect the progenitor star or to constrain its properties. Following image registration, we find that an isolated stellar object is not detected at the location of SN 2006my in either of the two pre-SN images. In the first, an I-band image obtained with the Wide-Field and Planetary Camera 2 on board the Hubble Space Telescope, the offset between the SN 2006my location and a detected source ("Source 1") is too large: > 0.08", which corresponds to a confidence level of non-association of 96% from our most liberal estimates of the transformation and measurement uncertainties. In the second, a similarly obtained V-band image, a source is detected ("Source 2") that has overlap with the SN 2006my location but is definitively an extended object. Through artificial star tests carried out on the precise location of SN 2006my in the images, we derive a 3-sigma upper bound on the luminosity of a red supergiant that could have remained undetected in our pre-SN images of log L/L_Sun = 5.10, which translates to an upper bound on such a star's initial mass of 15 M_Sun from the STARS stellar evolutionary models. Although considered unlikely, we can not rule out the possibility that part of the light comprising Source 1, which exhibits a slight extension relative to other point sources in the image, or part of the light contributing to the extended Source 2, may be due to the progenitor of SN 2006my. Only additional, high-resolution observations of the site taken after SN 2006my has faded beyond detection can confirm or reject these possibilities.Comment: Minor text changes from Version 1. Appendix added detailing the determination of confidence level of non-association of point sources in two registered astronomical image

Desmin mediates TNF-α–induced aggregate formation and intercalated disk reorganization in heart failure

We explored the involvement of the muscle-specific intermediate filament protein desmin in the model of tumor necrosis factor α (TNF-α)–induced cardiomyopathy. We demonstrate that in mice overexpressing TNF-α in the heart (α–myosin heavy chain promoter-driven secretable TNF-α [MHCsTNF]), desmin is modified, loses its intercalated disk (ID) localization, and forms aggregates that colocalize with heat shock protein 25 and ubiquitin. Additionally, other ID proteins such as desmoplakin and β-catenin show similar localization changes in a desmin-dependent fashion. To address underlying mechanisms, we examined whether desmin is a substrate for caspase-6 in vivo as well as the implications of desmin cleavage in MHCsTNF mice. We generated transgenic mice with cardiac-restricted expression of a desmin mutant (D263E) and proved that it is resistant to caspase cleavage in the MHCsTNF myocardium. The aggregates are diminished in these mice, and D263E desmin, desmoplakin, and β-catenin largely retain their proper ID localization. Importantly, D263E desmin expression attenuated cardiomyocyte apoptosis, prevented left ventricular wall thinning, and improved the function of MHCsTNF hearts

Assessment of preoperative accelerated radiotherapy and chemotherapy in stage IIIa (N2) non-small-cell lung cancer

AbstractForty patients with N2 non-small-cell lung cancer (stage IIIA), as determined by mediastinoscopy, were entered into a preoperative neoadjuvant study of chemotherapy (platinum, 5-fluorouracil, vinblastine) and accelerated radiotherapy (150 cGy twice per day for 7 days) for two cycles. Surgical resection was then performed and followed up with an additional cycle of chemotherapy and radiotherapy. All patients completed preoperative therapy. A major clinical response was seen in 87% of patients. Thirty-five patients underwent resection (one preoperative death, one refused operation, one had deterioration of pulmonary function, and two had pleural metastases). Operative mortality rate was 5.7% (2/35). Sixty percent of patients had no complications. Major complications included pulmonary emboli (three), pneumonia (two), and myocardial infarction (one). Downstaging was seen in 46% of patients, with two patients (5.7%) having no evidence of tumor in the specimen, five patients having sterilization of all lymph nodes, and nine patients having sterilization of mediastinal nodes but positive N1 nodes. Median survival of 40 patients was 28 months, with a projected 5-year survival of 43%. Patients with downstaged disease had statistically significant improved survival compared with patients whose disease was not downstaged. (J THORAC CARDIOVASC SURG 1996;111:123-33

Omentum is highly effective in the management of complex cardiothoracic surgical problems

AbstractObjectives: Vascularized, pedicled tissue flaps are often used for cardiothoracic surgical problems complicated by factors that adversely affect healing, such as previous irradiation, established infection, or steroid use. We reviewed our experience with use of the omentum in these situations to provide a yardstick against which results with other vascularized flaps (specifically muscle flaps) could be compared. Methods: A retrospective review was undertaken of 85 consecutive patients in whom omentum was used in the chest. In 47 patients (group I), use of omentum was prophylactic to aid in the healing of closures or anastomoses considered to be at high risk for failure. In 32 patients (group II), omentum was used in the treatment of problems complicated by established infection. In 6 patients (group III), omentum was used for coverage of prosthetic chest wall replacements after extensive chest wall resection. Results: Overall, omental transposition was successful in its prophylactic or therapeutic purpose in 88% of these difficult cases (75/85). Success with omentum was achieved for 89% of patients (42/47) in group I, 91% of patients (29/32) in group II, and 67% of patients (4/6) in group III. Three patients (3.5%) had complications of omental mobilization. Four patients (4.7%) died after the operation as a result of failure of the omentum to manage the problem for which it was used. Conclusions: Results with omental transposition compare favorably with published series of similarly challenging cases managed with muscle transposition. Complications of omental mobilization are rare. We believe that its unique properties render the omentum an excellent choice of vascularized pedicle in the management of the most complex cardiothoracic surgical problems.J Thorac Cardiovasc Surg 2003;125:526-3

Anastomotic complications after tracheal resection: Prognostic factors and management

ObjectiveWe sought to identify risk factors for anastomotic complications after tracheal resection and to describe the management of these patients.MethodsThis was a single-institution, retrospective review of 901 patients who underwent tracheal resection.ResultsThe indications for tracheal resection were postintubation tracheal stenosis in 589 patients, tumor in 208, idiopathic laryngotracheal stenosis in 83, and tracheoesophageal fistula in 21. Anastomotic complications occurred in 81 patients (9%). Eleven patients (1%) died after operation, 6 of anastomotic complications and 5 of other causes (odds ratio 13.0, P = .0001 for risk of death after anastomotic complication). At the end of treatment, 853 patients (95%) had a good result, whereas 37 patients (4%) had an airway maintained by tracheostomy or T-tube. The treatments of patients with an anastomotic complication were as follows: multiple dilations (n = 2), temporary tracheostomy (n = 7), temporary T-tube (n = 16), permanent tracheostomy (n = 14), permanent T-tube (n = 20), and reoperation (n = 16). Stepwise multivariable analysis revealed the following predictors of anastomotic complications: reoperation (odds ratio 3.03, 95% confidence interval 1.69-5.43, P = .002), diabetes (odds ratio 3.32, 95% confidence interval 1.76-6.26, P = .002), lengthy (≥4 cm) resections (odds ratio 2.01, 95% confidence interval 1.21-3.35, P = .007), laryngotracheal resection (odds ratio 1.80, 95% confidence interval 1.07-3.01, P = .03), age 17 years or younger (odds ratio 2.26, 95% confidence interval 1.09-4.68, P = .03), and need for tracheostomy before operation (odds ratio 1.79, 95% confidence interval 1.03-3.14, P = .04).ConclusionsTracheal resection is usually successful and has a low mortality. Anastomotic complications are uncommon, and important risk factors are reoperation, diabetes, lengthy resections, laryngotracheal resections, young age (pediatric patients), and the need for tracheostomy before operation