Low-loss reciprocal optical terminals for two-way time-frequency transfer.

We present the design and performance of a low-cost, reciprocal, compact free-space terminal employing tip/tilt pointing compensation that enables optical two-way time-frequency transfer over free-space links across the turbulent atmosphere. The insertion loss of the terminals is ∼1.5 dB with total link losses of 15 dB, 24 dB, and 50 dB across horizontal, turbulent 2-km, 4-km, and 12-km links, respectively. The effects of turbulence on pointing control and aperture size, and their influence on the terminal design, are discussed.

Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases.

We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year-old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58-year-old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein-Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation.

Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered.

Invited Article: A compact optically coherent fiber frequency comb.

We describe the design, fabrication, and performance of a self-referenced, optically coherent frequency comb. The system robustness is derived from a combination of an optics package based on polarization-maintaining fiber, saturable absorbers for mode-locking, high signal-to-noise ratio (SNR) detection of the control signals, and digital feedback control for frequency stabilization. The output is phase-coherent over a 1-2 µm octave-spanning spectrum with a pulse repetition rate of ∼200 MHz and a residual pulse-to-pulse timing jitter <3 fs well within the requirements of most frequency-comb applications. Digital control enables phase coherent operation for over 90 h, critical for phase-sensitive applications such as timekeeping. We show that this phase-slip free operation follows the fundamental limit set by the SNR of the control signals. Performance metrics from three nearly identical combs are presented. This laptop-sized comb should enable a wide-range of applications beyond the laboratory.

Comb-calibrated laser ranging for three-dimensional surface profiling with micrometer-level precision at a distance.

Non-contact surface mapping at a distance is interesting in diverse applications including industrial metrology, manufacturing, forensics, and artifact documentation and preservation. Frequency modulated continuous wave (FMCW) laser detection and ranging (LADAR) is a promising approach since it offers shot-noise limited precision/accuracy, high resolution and high sensitivity. We demonstrate a scanning imaging system based on a frequency-comb calibrated FMCW LADAR and real-time digital signal processing. This system can obtain three-dimensional images of a diffusely scattering surface at stand-off distances up to 10.5 m with sub-micrometer accuracy and with a precision below 10 µm, limited by fundamental speckle noise. Because of its shot-noise limited sensitivity, this comb-calibrated FMCW LADAR has a large dynamic range, which enables precise mapping of scenes with vastly differing reflectivities such as metal, dirt or vegetation. The current system is implemented with fiber-optic components, but the basic system architecture is compatible with future optically integrated, on-chip systems.

Clinicopathologic characteristics and survival outcomes of patients with advanced esophageal, gastroesophageal junction, and gastric adenocarcinoma: a single-institution experience.

UNLABELLED: Most patients with gastric or gastroesophageal junction (gej) cancer are diagnosed with inoperable advanced or metastatic disease. In these cases, chemotherapy is the only treatment demonstrating survival benefit. The present study compares clinicopathologic characteristics and survival outcomes for patients with advanced esophageal, gej, and gastric adenocarcinoma treated with first-line chemotherapy [epirubicin-cisplatin-5-fluorouracil (ecf), epirubicin-cisplatin-capecitabine (ecx), or etoposide-leucovorin-5-fluorouracil (elf)] or best supportive care (bsc) at our institution with those for historical controls. METHODS: We retrospectively reviewed medical information for 401 patients with newly diagnosed advanced esophageal, gej, or gastric adenocarcinoma treated with first-line chemotherapy (ecf, ecx, or elf) or bsc from January 1, 2004, through December 31, 2010. Descriptive statistics were used to compare the data collected with data for historical control patients. RESULTS: Of the study patients, 93% were diagnosed with metastatic disease (n = 374), and 63% received bsc only (n = 251). The main reasons that patients received bsc only included poor Eastern Cooperative Oncology Group performance status (55%), patient decision (31%), and comorbidities (14%). Of the remaining patients, 98 (24%) received ecf or ecx and 52 (13%) received elf as first-line treatment. Median overall survival was significantly longer in patients treated with ecf or ecx or with elf than in those receiving bsc (12.7 months vs. 12.7 months vs. 5.5 months respectively). Chemotherapy also significantly reduced the risk of death (64% reduction with ecf or ecx, 58% with elf). CONCLUSIONS: We confirmed the substantial overall survival benefit of combination chemotherapy compared with bsc, with better survival in our patient population than in historical controls. However, novel treatment options are still warranted to improve outcomes in this patient population.

Low-dose inhaled and nasal corticosteroid use and the risk of cataracts.

Orally inhaled corticosteroid use has been convincingly linked to an increase in the risk of cataracts, although the risk at lower doses in common use remains uncertain. The potential risk of cataracts with the use of nasal corticosteroids is unknown. A matched nested case-control analysis was performed in a population-based cohort of elderly people who had been dispensed medications for airway disease, as identified through a universal drug benefit plan. Inhaled corticosteroid use was associated with a dose-related increase in both the risk of all cataracts and severe cataracts requiring extraction, and the increase in risk of severe cataracts was apparent even at daily doses of

Ahmed valve implantation in glaucoma secondary to chronic uveitis.

PURPOSE: To evaluate the efficacy of Ahmed valve (AV) implantation in patients with uveitic glaucoma. METHODS: In total, 18 patients (19 eyes) with glaucoma secondary to chronic uveitis, who underwent AV implantation were retrospectively reviewed. Visual acuity, intraocular pressure (IOP), and glaucoma medications at the most recent examination prior to surgery, were compared with those of last postoperative examination. The surgical success was defined as IOP less than 21 mmHg and greater than 4 mmHg without loss of light perception and visually devastating complications at the last postoperative examination. Decrease in the number of glaucoma medications was also a criterion for surgical success. RESULTS: The mean follow-up period was 26+/-9.7 months. The mean preoperative and postoperative IOPs were 33.3+/-9.7 (range, 20-57) mmHg and 17.3+/-10.8 (range, 6-40) mmHg respectively (P<0.0001). The mean number of antiglaucoma medications was 3.5+/-0.8 (range, 2-5) preoperatively and 1.4+/-1.3 (range, 0-4) postoperatively (P<0.0001). Valve occlusion (five eyes, 26.3%) was the most commonly observed complication. Surgical success was achieved in 13 eyes (68.4%). The cumulative probability of success was 94.4% at 1 year and 60% at 2 years. Five eyes (26.3%) with IOP greater than 21 mmHg and one (5.3%) with corneal decompensation requiring penetrating keratoplasty were considered as failures. CONCLUSIONS: The implantation of AV is an effective surgical procedure for the management of uveitic glaucoma. The inflammatory background might contribute to the occurrence of valve occlusion, which is the most common complication. Prevention of this complication is an essential factor for improving the surgical outcome.

The role of ultrasound biomicroscopy in predicting the result of temporal artery biopsy in temporal arteritis patients: a preliminary study.

PURPOSE: Temporal artery biopsy is considered the gold standard for the diagnosis of temporal arteritis (TA). However, complications following this procedure may occur. The goal of this study is to evaluate if ultrasound biomicroscope (UBM) findings are useful in predicting the result (positive or negative) of temporal artery biopsy in patients with TA. METHODS: Twenty-six consecutive patients with clinical diagnosis of TA seen at the Department of Ophthalmology, Royal Victoria Hospital, Montreal, Canada, were involved in this study. All patients were submitted to UBM before temporal artery biopsy. Eight patients presented histopathologic findings consistent with the diagnosis of TA. Thus, UBM findings of these patients were compared with those from 18 patients with negative biopsy. On UBM we searched for the presence of a hypoechoic effect surrounding the walls of the temporal arteries, the so-called halo sign, as well as an intra-arterial middle reflexive filling, the so-called intra-arterial filling. RESULTS: The halo sign and/or the intra-arterial filling were found in 8 (100%) of 8 patients with biopsy-proven TA. However, 10 (55.5%) of 18 patients with a negative biopsy presented one or both of these two UBM findings. On the other hand, the absence of these two parameters on the UBM of a patient with TA strongly suggests that the temporal artery biopsy will be negative (negative predictive value=100%). CONCLUSIONS: This preliminary work suggests that UBM may play a role in predicting a negative result of the temporal artery biopsy in patients with TA. In the present series approximately 30% of the patients could be spared this surgical procedure and its possible complications.

The role of ultrasound biomicroscopy in predicting the result of temporal artery biopsy in temporal arteritis patients: A preliminary study.

PURPOSE: Temporal artery biopsy is considered the gold standard for the diagnosis of temporal arteritis (TA). However, complications following this procedure may occur. The goal of this study is to evaluate if ultrasound biomicroscope (UBM) findings are useful in predicting the result (positive or negative) of temporal artery biopsy in patients with TA. METHODS: Twenty-six consecutive patients with clinical diagnosis of TA seen at the Department of Ophthalmology, Royal Victoria Hospital, Montreal, Canada, were involved in this study. All patients were submitted to UBM before temporal artery biopsy. Eight patients presented histopathologic findings consistent with the diagnosis of TA. Thus, UBM findings of these patients were compared with those from 18 patients with negative biopsy. On UBM we searched for the presence of a hypoechoic effect surrounding the walls of the temporal arteries, the so-called halo sign, as well as an intra-arterial middle reflexive filling, the so-called intra-arterial filling. RESULTS: The halo sign and/or the intra-arterial filling were found in 8 (100%) of 8 patients with biopsy-proven TA. However, 10 (55.5%) of 18 patients with a negative biopsy presented one or both of these two UBM findings. On the other hand, the absence of these two parameters on the UBM of a patient with TA strongly suggests that the temporal artery biopsy will be negative (negative predictive value=100%). CONCLUSIONS: This preliminary work suggests that UBM may play a role in predicting a negative result of the temporal artery biopsy in patients with TA. In the present series approximately 30% of the patients could be spared this surgical procedure and its possible complications.

Multifocal choroiditis--an unusual finding in Crohn's disease.

PURPOSE: To report a patient with Crohn's disease and acute decreased vision in one eye secondary to multifocal choroiditis and serous retinal detachment. METHODS: A complete ocular examination, including fluorescein angiography, was performed. RESULTS: Fundus biomicroscopy disclosed multifocal, deep, discretely elevated yellowish lesions at the posterior pole of the affected eye. Fluorescein angiographic study of these lesions revealed early hypofluorescence followed by late hyperfluorescence. Subtenonian injection of corticosteroids rapidly induced remission of the choroidal lesions. CONCLUSIONS: Chorioretinal involvement in patients with Crohn's disease may or may not be related to reactivation of this disorder. Therefore, even patients without gastrointestinal symptoms who present with posterior segment inflammation must be informed of this. The chorioretinal inflammatory lesions do seem to respond promptly to periocular injection of corticosteroids.

Germline truncating mutations in both MSH2 and BRCA2 in a single kindred.

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.

Ultrasound biomicroscopic evaluation of the traumatized eyes.

PURPOSE: To review causes for performing an ultrasound biomicroscopic (UBM) examination in traumatized eyes, to present common UBM findings of 109 eyes with a history of ocular trauma and to compare these findings according to the type of the trauma. MATERIALS AND METHODS: A total of 109 eyes with a history of mechanical ocular trauma, which underwent an UBM examination between December 1996 and April 2002, were evaluated retrospectively. All cases were classified according to the criteria of the Ocular Trauma Classification Group and UBM findings were reviewed. For statistical ana- lyses, chi(2) test and Fisher's exact test were used. RESULTS: UBM examinations were performed for the evaluation of the zonules before cataract surgery (49.5%), examination of the anterior segment in the presence of media opacities (32.1%), detection of suspected ocular foreign bodies (10.1%) and the evaluation of ocular hypotony (8.3%). In all, 67 eyes (61.5%) had a closed-globe injury, whereas 42 (38.5%) had an open-globe injury. The most common UBM findings in a closed-globe injury were zonular deficiency (64.2%), angle recession (43.3%), iridodialysis (17.9%), and dislocated lens (16.4%). The most common UBM findings in an open-globe injury were zonular deficiency (54.8%), iridodialysis (26.2%), peripheral anterior synechiae (PAS) (26.2%), and iridocorneal adhesion (19%). Among the common UBM findings, the angle recession was significantly higher (P<0.001) in closed-globe injury group and PAS formation was significantly higher (P<0.05) in open-globe injury group. CONCLUSIONS: UBM is particularly superior to other methods in the evaluation of the zonular status, angle recession, cyclodialysis, and the detection of small superficial and intraocular foreign bodies.

Racial bias in using USMLE step 1 scores to grant internal medicine residency interviews.

PURPOSE: To determine whether the United States Medical Licensing Examination (USMLE) Step 1 score, commonly used in screening residency applicants for interviews, eliminates a greater proportion of African-American applicants from the interview process at an internal medicine residency program. METHOD: A survey of internal medicine residency programs was performed to determine the prevalence of using USMLE Step 1 scores to grant interviews. A cohort of applicants was analyzed by constructing a database of USMLE Step 1 scores from the Electronic Residency Application Service (ERAS) database of applications from U.S., Canadian, and osteopathic medical schools to one residency program in 2000. Each applicant was classified as African American or non-African American. Rejection rates were then calculated for each five-point increment from a hypothetical threshold rejection score of <180 to <215. RESULTS: Responses were received from 259 residency programs (69%), and 92% used the USMLE Step 1 score in deciding which applicants to interview. A cohort of 626 non-African-American and 47 African-American applicants was analyzed. The proportion of applicants below each incremental threshold score was significantly higher for African-American applicants (p <.05 at each level). Depending on the threshold score used, an African-American applicant was three to six times less likely to be offered an interview. CONCLUSIONS: When USMLE Step 1 scores are used to screen applicants for a residency interview, a significantly greater proportion of African-American students will be refused an interview.

A state association approach to the policy and politics of the worker shortage.

In January 2000, the Board of Directors of the Home & Health Care Association (H&HCA), identified the issue of worker recruitment and retention as a "critical issue" in the Association's strategic plan. With a different perspective from its employer/agencies, the Association began to devote more resources (staff time) to the issue, tapping into what was already happening in the state and proposing some solutions of its own.

Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer.

The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies according to the age at diagnosis, family history of cancer, and ethnicity/country of origin. We set out to estimate the frequency of seven previously described founder mutations in BRCA1 and BRCA2 in all eligible French Canadian women diagnosed with invasive breast cancer at one Montreal hospital over a 20-month period. One hundred and ninety-two patients were eligible and 127 (66.2%) provided blood for genetic testing. We identified 4 women who carried a founder mutation (3.1%, 95% confidence interval 0.9-7.9%) in this population. Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for mutation carriers was 51.2 years (range 49.1-53.5). Two of these 4 cases were lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or 2. Despite a small tumor size (< or =20 mm), axillary nodal involvement was present in 3 women. Estrogen receptors were strongly expressed in all cases. Two of the 4 cases reported a strong family history of breast cancer, but a family history of site-specific breast cancer was a relatively poor indicator of the presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of chance, but may also reflect different geographical origins of the most common BRCA1 mutations within the French Canadian population.

Agonistic induction of a covalent dimer in a mutant of natriuretic peptide receptor-A documents a juxtamembrane interaction that accompanies receptor activation.

The natriuretic peptide receptor-A (NPR-A) is composed of an extracellular domain with a ligand binding site, a transmembrane-spanning domain, a kinase homology domain, and a guanylyl cyclase domain. In response to agonists (atrial natriuretic peptide (ANP) and brain natriuretic peptide), the kinase homology domain-mediated guanylate cyclase repression is removed, which allows the production of cyclic GMP. Previous work from our laboratory strongly indicated that agonists are exerting their effects through the induction of a juxtamembrane dimeric contact. However, a direct demonstration of this mechanism remains to be provided. As a tool, we are now using the properties of a new mutation, D435C. It introduces a cysteine at a position in NPR-A corresponding to a supplementary cysteine found in NPR-C6, another receptor of this family (a disulfide-linked dimer). Although this D435C mutation only leads to trace levels of NPR-A disulfide-linked dimer at basal state, covalent dimerization can be induced by a treatment with rat ANP or with other agonists. The NPR-A(D435C) mutant has not been subjected to significant structural alterations, since it shares with the wild type receptor a similar dose-response pattern of cellular guanylyl cyclase activation. However, a persistent activation accompanies NPR-A(D435C) dimer formation after the removal of the inducer agonist. On the other hand, a construction where the intracellular domain of NPR-A(D435C) has been truncated (DeltaKC(D435C)) displays a spontaneous and complete covalent dimerization. In addition, the elimination of the intracellular domain in wild type DeltaKC and DeltaKC(D435C) is associated with an increase of agonist binding affinity, this effect being more pronounced with the weak agonist pBNP. Also, a D435C secreted extracellular domain remains unlinked even after incubation with rat ANP. In summary, these results demonstrate, in a dynamic fashion, the agonistic induction of a dimeric contact in the juxtamembrane domain of NPR-A. In addition, this process seems to require membrane attachment of the receptor. Finally, the intracellular domain represses this contact at the basal state, showing its potent influence on the outer juxtamembrane domain.

Safety and efficacy comparison of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects with allergic conjunctivitis. Emadine Study Group.

PURPOSE: To determine the efficacy and tolerance of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects. METHODS AND MATERIALS: In a randomized, double-masked, parallel controlled study, emedastine 0.05% ophthalmic solution BID was compared to levocabastine 0.05% ophthalmic suspension BID, for control of the signs and symptoms of allergic conjunctivitis in pediatric subjects ages 3-16. Subjects who met all inclusion and exclusion criteria received masked study medication with instructions to instill drops twice daily, in the morning and evening. A diary was completed by the parents four times daily for the first two and last two weeks of the study. Treatment lasted 42 days. Drug efficacy was assessed at the initial administration in the office at Day 0 and after 3, 7, 14, 30 and 42 days. RESULTS: Overall results showed both drugs have an effect and that emedastine was significantly superior (p < 0.05) to levocabastine for the relief of chemosis on Days 14, 30 and 42; of itching on follow-up Days 30 and 42 (p < 0.05); of redness on Days 30 and 42; for eyelid swelling on Days 14 and 30; and for physician's impression score on Days 7, 14, 30 and 42. CONCLUSION: These results confirm previous preclinical and clinical data on the potent and long acting efficacy of this promising new ophthalmic anti-allergic drug, emedastine in pediatric subjects.

An efficacy and tolerance comparison of emedastine difumarate 0.05% and levocabastine hydrochloride 0.05%: reducing chemosis and eyelid swelling in subjects with seasonal allergic conjunctivitis. Emadine Study Group.

PURPOSE: To compare emedastine ophthalmic solution 0.05% BID to levocabastine ophthalmic suspension 0.05% BID in reducing chemosis, eyelid swelling and other signs and symptoms in subjects with seasonal allergic conjunctivitis. METHODS: In a randomized, double-masked, parallel controlled study, emedastine ophthalmic solution 0.05% BID was compared to levocabastine ophthalmic suspension 0.05% BID for control of chemosis, eyelid swelling and other parameters in the environmental allergy study model. RESULTS: At Days 7, 14, 30 and 42, emedastine was significantly better than levocabastine at controlling chemosis and eyelid swelling (p < 0.05). A statistical trend was seen at Day 3 (0.05 < p < 0.10). Results were clinically relevant at Days 30 and 42. Emedastine was also significantly better at reducing redness and itching at Days 7, 14, 30 and 42 (p < 0.05). CONCLUSION: Emedastine is more efficacious than levocabastine in reducing chemosis, eyelid swelling and other efficacy variables associated with seasonal allergic conjunctivitis.