Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Reproductive and developmental toxicity assessment of palbociclib, a CDK4/6 inhibitor, in Sprague-Dawley rats and New Zealand White rabbits.

Palbociclib is a selective inhibitor of the cyclin-dependent kinase (CDK) 4/6, approved for the treatment of breast cancer. We assessed the potential effects of oral administration of palbociclib on reproduction and development. There were no effects on female or male fertility indices; however, in the male there was seminiferous tubule degeneration in the testes and secondary findings in the epididymides, lower testicular and epididymal weights, sperm density and motility. Palbociclib was not teratogenic in rats or rabbits; however, in the presence of maternal toxicity (lower maternal body weight gain and food consumption), low fetal body weights were observed in rats and small forepaw phalanges were noted in rabbits. There were, however, no adverse effects on the F1 generation in a pre- and post-natal developmental toxicity study in the rat.

PIFA-mediated ethoxyiodination of enamides with potassium iodide.

The regioselective ethoxyiodination of enamides was developed using PIFA in combination with potassium iodide in ethanol. The reaction proceeds regioselectively with excellent yields and diastereoselectivities, providing valuable synthons for further functionalisations. Control experiments were conducted, indicating that the transformation occurs through an ionic manifold involving an in situ generated hypoiodite species.

Needles of light produced with a spherical mirror.

We describe how laterally confined and axially stretched needles of light can be produced by focusing a radially polarized annular optical beam with a spherical mirror. Our analysis is based on an extension of the Richards-Wolf formalism appropriate for nonaplanetic focusing systems operated under nonparaxial conditions. While maintaining their lateral confinement near the theoretical limit of 0.36λ, the needles of light that are produced can extend axially over 1000's of λ, in full compliance with geometrical and electromagnetic considerations. Relationships are established between the thickness of the incident annular beam and the length of the needle of light.

Purification, characterization and amino acid sequencing of divergicin M35: a novel class IIa bacteriocin produced by Carnobacterium divergens M35.

Carnobacterium divergens M35, isolated from a commercial sample of frozen smoked mussels, produces a new bacteriocin, divergicin M35, a class IIa bacteriocin. Divergicin M35 is sensitive to pronase-E, alpha-chymotrypsin and proteinase K, but not to trypsin and withstands thermal treatments up to 121 degrees C for 30 min. Divergicin M35 was extracted from the culture supernatant of C. divergens M35 using an SP-Sepharose cation-exchange column, desalted and purified on a C18 Sep-Pack column and further purified by reverse phase-high pressure liquid chromatography. This procedure allowed the recovery of 10% of the bacteriocin present in the culture supernatant with purity higher than 99%. Divergicin M35 had a molecular mass of 4518.75 Da as determined by mass spectrometry, a pI value of 8.3 and positive net charge (+3). The amino acid sequence of divergicin M35 was found to consist of 43 amino acid with four cysteine residues (Cys10, 15, 25, 43) and showed 80.5% homology with divercin V41 (80.5%) and 80.0% with bavaricin MN. Divergicin M35 showed powerful antilisterial activity, especially against Listeria monocytogenes and was also active against carnobacteria but not against strains of Lactococcus, Lactobacillus, Enterococcus, Bifidobacteria and Escherichia. Divergicin M35 production began in late exponential phase and reached a maximum activity of 65,000 AU/ml in early stationary phase. Initial broth pH, Tween 80 and acetate did not affect C. divergens M35 growth or divergicin production. This bacteriocin may be a potential tool for inhibiting L. monocytogenes in seafood products that do not usually undergo an adequate heat treatment.

Acute toxicity of local anesthetic ropivacaine and mepivacaine during a combined lumbar plexus and sciatic block for hip surgery.

Hip fracture is a common pathology in elderly patients. Intercurrent diseases, mainly cardiac and respiratory, often result in significant morbidity and mortality. Anesthesia for hip fracture can be provided by general or regional techniques. The combination of a lumbar plexus and posterior sciatic nerve block represents an alternative to neuraxial technique of anaesthesia such as spinal anesthesia (4, 6). We report a case of acute toxicity resulting in the injection of local anesthetics Ropivacaine and Mepivacaine in elderly patient. An elderly woman was scheduled for surgical repair of a fractured femur neck by dynamic hip screw synthesis. Anesthesia was realized by peripheral nerve bi-block (lumbar plexus and posterior sciatic block) (7). The patient experienced seizures and dysrhythmias twenty minutes after block completion and injection of the anesthetic solution [Ropivacaine 0.75%, administered for lumbar plexus block performed via the posterior approach (WINNIE) and Mepivacaine 1.5%, administered for posterior sciatic nerve block (LABAT)]. Cardiopulmonary resuscitation was successful. All signs of toxicity disappeared after injection of midazolam and atropine, intubation and 100% oxygen ventilation. We decided to proceed with surgery. The postoperative course was uncomplicated and made a full recovery.

[Perturbations of activities of daily living in Alzheimer's disease. A study of 172 patients with the using a questionnaire completed by caregivers]. / Perturbations des activités quotidiennes au cours de la maladie d'Alzheimer. Etude chez 172 patients à l'aide d'un questionnaire rempli par le conjoint.

Functional decline was studied retrospectively in 172 patients with Alzheimer's disease, AD, using a questionnaire completed by the caregiver. Ninety-nine of these patients had a second assessment after a follow-up of 22.1 +/- 13.8 months. The questionnaire included French versions of the Physical Self-Maintenance Activities, ADL, and of the Instrumental Activities of Daily Living, IADL (Lawton and Brody, 1969). A third part assessing social activities, SADL, was derived from Katz and Lyerly (1963). The earliest and most frequent perturbations in early AD involved SADL, mainly a reduction in social and leisure activities, appearing in subjects with a MMSE score > 26. The earliest decline in IADL involved the ability for handling finances, odd jobs-sewing, and shopping, which were more frequently perturbed than ability to use telephone, traveling or handling medication. The most interesting results of our study were as follows. Functional decline did not allow to distinguish patients with early AD (MMSE score > or = 24) from those with mild dementia (MMSE score 20-23). Mild perturbations of ADL, mainly dressing and walking, were observed in early AD. There was a good correlation, but no parallelism, between functional decline and cognitive decline. Disturbances in ADL and SADL significantly differed only between patients with severe dementia (MMSE < 10) and those of the three other groups. Apathy appeared to be a stronger predictor of functional decline than the score on the MMSE in the early stages of AD. There was a great variability among the patients regarding the type of functional decline as well as the rate of decline. Functional decline is very useful for detecting early AD. However, its specificity seems to be low and the diagnosis should be supported by cognitive assessment.

Validation of the AmpFlSTR Profiler Plus PCR amplification kit for use in forensic casework.

According to TWGDAM guideline 4.5 (1), prior to implementing a new DNA analysis procedure or an existing DNA analysis procedure developed by another laboratory, the forensic laboratory must first demonstrate reliability of the procedure in-house. Seven phases were designed to validate the use of the AmpFlSTR Profiler Plus PCR Amplification Kit, as well as the PE Applied Biosystems 310 Genetic Analyzer. This report summarizes the results obtained for each of the seven phases of the validation study which included the following evaluations: polymer, reproducibility, sensitivity, stutter, precision, mixtures and nonprobative casework.

[Noncognitive symptoms in Alzheimer's disease. A study of 150 community-dwelling patients using a questionnaire completed by the caregiver]. / Les manifestations non cognitives de la maladie d'Alzheimer. Etude de 150 cas à l'aide d'un questionnaire rempli par le conjoint.

UNLABELLED: We studied the noncognitive symptoms in 150 community-dwelling Alzheimer's patients using a questionnaire completed by the caregiver, the Echelle Psychopathologique de la Démence de Type Alzheimer, EPDTA (Psychopathologic Scale of Dementia of Alzheimer Type). EPDTA is a 44-item questionnaire derived from the BEHAVE-AD and the Depressive Mood Scale, covering many aspects of the behavior, affective and psychiatric disturbances. Each item is rated from 0 (never observed) to 6 (most of the time). Frequency (percentage of symptom present) and severity (mean score when the symptom was present) were assessed for each item. The cognitive status and severity of the disease were assessed by the MMSE and two scales completed by the caregiver assessing the Activities of Daily Living scale (ADL) and the Cognitive Difficulties Scale (CDS). Noncognitive symptoms were present in all patients but remained moderate in severity. A principal component analysis of the 33 items exploring the affective disturbances showed seven clinically relevant factors: apathy, anxiety, anosognosia-irritability, euphoria, dysphoria, emotional incontinence and agitation. The most frequent noncognitive symptoms were the affective disturbances, especially apathy, and the sexual behavioural disturbances. No correlation were found between the overall severity of behavioural disturbances and cognitive status, duration of the disease nor demographic variables. However, a slight negative correlation was found between scores on apathy and on the MMSE. A second evaluation was performed in 59 patients after a mean follow-up of 18,2 months. The patients showed a progression of the disease evidenced by the scores on the MMSE, ADL and CDS scales. However, the frequency and severity of the noncognitive symptoms remained identical except for eating disorders, psychotic symptoms and agitation which were more frequent at the second examination and negatively correlated with the MMSE score. Most patients showed affective disturbances and scored high for apathy and anxiety-emotional incontinence dimensions. Like in a previous study, we found a double dissociation between these two dimensions in some patients, suggesting that they depend from different mechanisms. Agressivity, mostly verbal, was found in three quarters of the patients and was correlated to apathy, anosognosia and psychotic symptoms. CONCLUSION: The relationship between noncognitive manifestations and cognitive deficits in AD is not clear, suggesting that they depend from different biological and psychological mechanisms. Various dimensions may be described in the behavioural disturbances but their relationship with hypothetical biological mechanisms remains difficult. Our study stresses the importance of apathy, which was corelated with various noncognitive psychobehavioral manifestations in AD patients.

Apraxic disturbances in patients with mild to moderate Alzheimer's disease.

Twenty-two patients meeting the NINCDS-ADRDA diagnostic criteria for probable AD were included in the study, along with 10 matched controls. Praxic disturbances were investigated using eight tasks and the results were interpreted according to the neuropsychological model of Roy and Square modified by Rothi et al. (1988) [Aphasiology 21:381-388] which distinguishes a conceptual system concerned with knowledge of the action and function of gestures and a production system that effects gestures in the environment. Disturbance of the production system was found only in 17 patients. Disturbance of the production system was correlated to disturbance of verbal comprehension. The patients scored lower using the left hand than the right. Disturbance of the conceptual system was found in all patients and was not significantly correlated with other cognitive deficits. No significant difference in results was found according to the type of input to the conceptual system (visual or verbal). Deficits in tasks using real objects were correlated to disturbances of both the production and conceptual systems. Most patients performed poorly both in tasks exploring the conceptual system and in those exploring the production system. However, two patients performed badly in production tasks but had performances in the range of controls for conceptual tasks and one patient had the opposite pattern of dissociation. This provides evidence that the production and the conceptual system are independent. Impairment in the ability to perform everyday activities was correlated to disturbances of the conceptual system whereas poor performances in tasks exploring the production system or in using real objects were not.

Experimental transmission of porcine circovirus type 2 (PCV2) in weaned pigs: a sequential study.

Weaned specific pathogen-free pigs were inoculated intranasally with porcine circovirus type 2 (PCV2) and killed in groups of two or three animals at 6, 13, 20, 27 and 34 days post-inoculation (dpi), together with appropriate uninfected controls, for examination by histopathological, immunohistochemical (immunogold silver staining; IGSS), polymerase chain reaction (PCR) and viral isolation techniques. Serum samples were also collected for detection of antibodies. No major clinical signs were observed in infected pigs, and gross lesions were essentially limited to the lungs and lymph nodes of some of the animals. Histologically, no lesions were seen at 6 dpi, but bronchointerstitial pneumonia was invariably noted from 13 dpi onwards. Granulomatous inflammation, with or without intracytoplasmic inclusions, was present in lymphoid tissues (e.g. lymph nodes, thymus, spleen and tonsil) from day 20 onwards, being most severe at days 20 and 27 dpi. Liver inflammation was present at days 13, 20 and 27 dpi. Virus was demonstrated in the tissues by isolation and PCR methods throughout the experiment. PCV2 antigens were detected by IGSS in bronchial and bronchiolar epithelial cells, in mononuclear cells and multinucleated giant cells within inflammatory lesions, and in mononuclear cells of apparently normal tissues (e.glamina propria of the small intestine and the bronchus-associated lymphoid tissue). The lesions were consistent with those of postweaning multisystemic wasting syndrome (PMWS), although not all previously reported PMWS lesions were seen. PCV2 antibodies were detected in infected pigs from day 13 onwards. The results demonstrated widespread distribution of PCV2 after infection and persistence of the virus in vivo for at least 34 days. It would appear that PCV2 can induce PMWS lesions in weaned pigs in the absence of porcine parvovirus and other common swine pathogens.

Germ-line transformation of pink bollworm (Lepidoptera: gelechiidae) mediated by the piggyBac transposable element.

The pink bollworm, Pectinophora gossypiella, is a world-wide pest of cultivated cotton. In certain growing regions populations are suppressed by a sterile release strategy. Efforts to improve the sterile insect technique as well as our understanding of lepidopteran biology could benefit greatly from a germ-line transformation system. We report transformation of pink bollworm with a piggyBac transposable element carrying the enhanced green flourescent protein (EGFP) marker gene. This vector-marker system resulted in recovery of transgenics at a rate of approximately 3.5%. Integration of the transforming construct that was typical of piggyBac was demonstrated by Southern analysis and sequence determination of transposon flanks. Expression of the EGFP marker was visualized by fluorescent microscopy and Western Blot analysis. Maintenance of transformed strains indicates that the transgene segregates in a Mendelian fashion and has been stable over fourteen generations to date.

Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type.

OBJECTIVE: To study the unawareness of cognitive deficits in patients with mild dementia of Alzheimer type (DAT). DESIGN: Retrospective study. We surveyed the medical records of outpatients meeting the NINCDS-ADRDA criteria for probable DAT who were able to complete the Cognitive Difficulties Scale (CDS) and had a close informant relative (IR) who could complete the family form of the same questionnaire. SETTING: A department of neurology in a general teaching hospital. SUBJECTS: Eighty-eight patients, aged 73.2+/-8.6 years with a mean MMSE score of 22.5+/-3.2. Fifty-two of the 88 patients had a follow-up examination after a mean interval of 21 months. METHODS: Awareness of cognitive deficits was mainly assessed as the difference between the scores on the CDS completed by the IR and the patient (Index of Unawareness, IU). Two secondary assessments of unawareness were performed: (1) an assessment by the clinician on the basis of the patient's answers to questions probing the awareness of memory deficits; (2) an evaluation by the IR of the frequency of behavioural manifestations of unawareness in everyday life. SPECT was performed in 78 patients to study the relationship between unawareness and the topography of perfusion deficits. RESULTS: Awareness of the cognitive deficits varied greatly between patients, according to the assessment method used and the stage of progression of the disease. Most patients with mild DAT were cognitively aware of their cognitive deficits but failed to appraise their severity and their consequences in everyday life. Decreased awareness was positively correlated with age and perfusion deficits in the frontal regions and negatively with the anxious symptomatology. However, the main correlate of unawareness was apathy. CONCLUSION: The nature of unawareness of cognitive deficits appeared to be more dimensional than categorical. In patients with mild dementia, decreased awareness appeared to be more related to affective disturbances, especially to emotional deficit or apathy, than to cognitive deficits.

Memory complaints in young and elderly subjects.

OBJECTIVE: To compare the quantitative and qualitative aspects of memory complaints in cognitively normal subjects aged under and above 50 years. SETTING: A memory clinic located in a general hospital in a suburb of Paris offering direct access to subjects. DESIGN: Retrospective review of the files of consecutive patients who attended the clinic during one year. PARTICIPANTS: Subjects were included if (a) they presented with memory complaints, (b) they had normal general cognitive functioning according to age and educational level, (c) they were devoid of present or past history of neurologic or psychiatric disorders. METHODS: Subjects rated the severity of memory complaints as major or minor and filled in a 8-item questionnaire assessing various memory difficulties in everyday life. Relationship between severity of memory complaints and demographic data, memory performance and affective status was compared in 183 non-depressed, non-cognitively impaired healthy adults aged 50 years and over, and in 77 younger adults. RESULTS: Semiologic aspects and correlates of memory complaints were similar in younger and older adults. No close relationship was found between severity of memory complaints and memory performance. In both age groups, memory complaints were strongly related to affective status, mainly to the severity of anxious symptomatology. Memory complaints were related to gender in younger subjects, and to subjective assessment of well-being in older. CONCLUSION: Memory complaints of elderly do not appear basically different from memory complaints of younger subjects. They constitute a complex psychological symptom unlikely to be explained by a few variables and cannot be reduced to the subjective counterpart of memory performance decline associated with age.

Precise excision and transposition of piggyBac in pink bollworm embryos.

Transposable elements such as P, hobo, Hermes, mariner and Minos have been successfully harnessed as gene vectors to achieve the transformation of several dipteran species including Drosophila melanogaster, Ceratitis capitata and Aedes aegypti. Plasmid-based excision and transposition assays have been useful indicators of an element's ability to be mobilized in vivo and thus potentially serve as a transforming vector. We report that the transposable element piggyBac is capable of precise excision and transposition in the pink bollworm (Pectinophora gossypiella), a worldwide pest of cultivated cotton. Combined with a suitable marker gene, the piggyBac element may serve as a vector for germline transformation in this and (potentially) other lepidopteran species.

Telecentric three-dimensional sensor with a liquid mirror for large-object inspection.

We describe a device that applies the advantages of the space invariance of telecentric triangulation with the measurement of large objects (1 m(3)). Because the scan motion of the laser beam is decoupled from the physical transport of the sensor head, the fast scanning of large volumes becomes feasible. The device consists of a triangulation laser telemeter head that uses a large liquid primary mirror and an aspheric secondary mirror to realize the telecentric f-theta objective. We propose using liquid-mirror technology to make low-cost large objectives that have low f numbers, a diffraction-limited performance, and low scattering in the visible. This new optical system is useful for 3-D measurement. We discuss the optical configuration of the system and the performance of a laboratory prototype. The prototype has a standoff distance of 1.5 m, a telecentric scan as long as 1 m, a depth of view of 1 m, and a relative depth resolution of 0.5-1 mm.

Cutaneous and systemic necrotizing vasculitis in swine.

A systemic vasculitis involving particularly the skin and kidneys has been recently described in swine under the name dermatitis/nephropathy syndrome. Twelve pigs with gross cutaneous lesions typical of this condition were necropsied, and morphologic, immunohistochemical, microbiologic, and epidemiologic characteristics were studied. The pigs were divided into three groups comprising eight pigs with acute lesions, two with chronic lesions, and two with acute lesions kept for sequential skin biopsies. Acute skin lesions consisted of round to irregular, red to purple macules and papules that often coalesced to form large, irregular patches and plaques. With time, the lesions became covered by crusts and faded gradually, sometimes leaving scars. Characteristic distribution included the perineal area of the hindquarters, limbs, dependent parts of the abdomen and thorax, and margins of the ears. In the acute phase of the disease, necrotizing and leucocytoclastic vasculitis of small-caliber blood vessels were observed within the dermis and panniculus and in various extracutaneous locations such as the renal pelvis and synovial membranes. All pigs had macroscopic evidence of pneumonia and generalized lymphadenopathy. Microscopically, they had interstitial pneumonia and perivascular cuffing of mononuclear cells in various tissues including skin. The presence of immunoglobulins and complement was demonstrated by immunofluorescence in and around necrotic vessels of the skin in the early stages. Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) antigens were detected by immunohistochemistry in macrophages located around vessels of the tissues examined (skin and kidneys) in acute and chronic cases. PRRSV RNA was demonstrated by reverse transcription-polymerase chain reaction in lung and spleen homogenates from all pigs. The PRRSV was isolated in cell culture from 11 of the pigs. These findings suggest that PRRSV infection may play a role in the pathogenesis of this systemic vascular disease of swine.

Electromechanical microinjection of pink bollworm Pectinophora gossypiella embryos increases survival.

We report and compare methods and apparatus for injection of pink bollworm, Pectinophora gossypiella (Saunders), embryos. Injection with an electromechanical device resulted in 59% survival of embryos. Previous techniques relying on a mechanical manipulator resulted in 8% survival. Pink bollworm (PBW) embryo injection technology is based in part on methods developed for injection and genetic transformation of Caenorhabditis elegans ([Maupas] Dougherty) and Drosophila melanogaster (Meigen) with substantial alterations in both method and apparatus to accommodate special conditions of PBW biology, behavior and morphology. The microinjection methodology described here has direct application to other difficult-to-inject insects and invertebrates.