Memoir of Mrs. Sarah L. Huntington Smith, late of the American mission in Syria / by Edward W. Hooker.

http://www.archive.org/details/memoirofhuntingt00hookuoft

Late onset of huntington's disease

Twenty-five patients with late-onset Huntington's disease were studied; motor impairment appeared at age 50 years or later. The average age at onset of chorea was 57.5 years, with an average age at diagnosis of 63.1 years. Approximately 25% of persons affected by Huntington's disease exhibit late onset. A preponderance of maternal transmission was noted in late-onset Huntington's disease. The clinical features resembled those of mid-life onset Huntington's disease but progressed more slowly. Neuropathological evaluation of two cases reveal less severe neuronal atrophy than for mid-life onset disease.

Leaf galls in our native trees and shrubs

Plant galls constitute a branch of study and research which has been to me a subject of much interest for some time. At the start of this work, it was intended to include Plant galls in general, but after some months this was found to be too comprehensive a field and would in fact take a great many years to study fully. Even leaf galls alone, both of herbs and trees provide so large a field of investigation that ultimately I decided to confine my attention to those or our native trees and shrubs. Upon looking up the literature on this subject, it will be found that in nearly all cases, either the gall is described fully and mere mention made or the agent concerned in its production, or vice versa. This state of things is most unsatisfactory, as in studying galls, both the gall-maker and the gall formation must be examined in detail before it is safe to apply nomenclature. This work, therefore, sets out to give accurate and scientific descriptions of both galls and gall-makers. The difficulties encountered are manifold; firstly, our trees are all deciduous, hence, the collecting period is necessarily restricted to that time of the year between the appearance of the buds and the fall of the leaf. Secondly, the rearing of imagines is always difficult, especially in the case or the autumn gall; more will be said on this matter later. Lastly, due to war-time conditions much trouble was experienced in obtaining suitable literature and many invaluable books on this subject were unprocurable. The Plates at the back have all been copied from original material except in the case or the Phytoptid mites which have been sketched with the help of illustrations, the reason for this being the difficulty of making suitable mounts of these minute creatures, Where possible all stages or at least larva and imago have been sketched, together with the host plant and the type of gall-formation produced. Slides have also been made of most larvae and the imagines attached to cards and pinned on to pith or cork in the usual manner.

Integrated spot size converters for InP based photonic systems

The ever increasing demand for broadband communications requires sophisticated devices. Photonic integrated circuits (PICs) are an approach that fulfills those requirements. PICs enable the integration of different optical modules on a single chip. Low loss fiber coupling and simplified packaging are key issues in keeping the price of PICs at a low level. Integrated spot size converters (SSC) offer an opportunity to accomplish this. Design, fabrication and characterization of SSCs based on an asymmetric twin waveguide (ATG) at a wavelength of 1.55 μm are the main elements of this dissertation. It is theoretically and experimentally shown that a passive ATG facilitates a polarization filter mechanism. A reproducible InP process guideline is developed that achieves vertical waveguides with smooth sidewalls. Birefringence and resonant coupling are used in an ATG to enable a polarization filtering and splitting mechanism. For the first time such a filter is experimentally shown. At a wavelength of 1610 nm a power extinction ratio of (1.6 ± 0.2) dB was measured for the TE- polarization in a single approximately 372 μm long TM- pass polarizer. A TE-pass polarizer with a similar length was demonstrated with a TM/TE-power extinction ratio of (0.7 ± 0.2) dB at 1610 nm. The refractive indices of two different InGaAsP compositions, required for a SSC, are measured by the reflection spectroscopy technique. A SSC layout for dielectric-free fabricated compact photodetectors is adjusted to those index values. The development and the results of the final fabrication procedure for the ATG concept are outlined. The etch rate, sidewall roughness and selectivity of a Cl2/CH4/H2 based inductively coupled plasma (ICP) etch are investigated by a design of experiment approach. The passivation effect of CH4 is illustrated for the first time. Conditions are determined for etching smooth and vertical sidewalls up to a depth of 5 μm.

Ironworking in late medieval Ireland, c. AD. 1200 to 1600

The landscape of late medieval Ireland, like most places in Europe, was characterized by intensified agricultural exploitation, the growth and founding of towns and cities and the construction of large stone edifices, such as castles and monasteries. None of these could have taken place without iron. Axes were needed for clearing woodland, ploughs for turning the soil, saws for wooden buildings and hammers and chisels for the stone ones, all of which could not realistically have been made from any other material. The many battles, waged with ever increasingly sophisticated weaponry, needed a steady supply of iron and steel. During the same period, the European iron industry itself underwent its most fundamental transformation since its inception; at the beginning of the period it was almost exclusively based on small furnaces producing solid blooms and by the turn of the seventeenth century it was largely based on liquid-iron production in blast-furnaces the size of a house. One of the great advantages of studying the archaeology of ironworking is that its main residue, slag, is often produced in copious amounts both during smelting and smithing, is virtually indestructible and has very little secondary use. This means that most sites where ironworking was carried out are readily recognizable as such by the occurrence of this slag. Moreover, visual examination can distinguish between various types of slag, which are often characteristic for the activity from which they derive. The ubiquity of ironworking in the period under study further means that we have large amounts of residues available for study, allowing us to distinguish patterns both inside assemblages and between sites. Disadvantages of the nature of the remains related to ironworking include the poor preservation of the installations used, especially the furnaces, which were often built out of clay and located above ground. Added to this are the many parameters contributing to the formation of the above-mentioned slag, making its composition difficult to connect to a certain technology or activity. Ironworking technology in late medieval Ireland has thus far not been studied in detail. Much of the archaeological literature on the subject is still tainted by the erroneous attribution of the main type of slag, bun-shaped cakes, to smelting activities. The large-scale infrastructure works of the first decade of the twenty-first century have led to an exponential increase in the amount of sites available for study. At the same time, much of the material related to metalworking recovered during these boom-years was subjected to specialist analysis. This has led to a near-complete overhaul of our knowledge of early ironworking in Ireland. Although many of these new insights are quickly seeping into the general literature, no concise overviews on the current understanding of the early Irish ironworking technology have been published to date. The above then presented a unique opportunity to apply these new insights to the extensive body of archaeological data we now possess. The resulting archaeological information was supplemented with, and compared to, that contained in the historical sources relating to Ireland for the same period. This added insights into aspects of the industry often difficult to grasp solely through the archaeological sources, such as the people involved and the trade in iron. Additionally, overviews on several other topics, such as a new distribution map of Irish iron ores and a first analysis of the information on iron smelting and smithing in late medieval western Europe, were compiled to allow this new knowledge on late medieval Irish ironworking to be put into a wider context. Contrary to current views, it appears that it is not smelting technology which differentiates Irish ironworking from the rest of Europe in the late medieval period, but its smithing technology and organisation. The Irish iron-smelting furnaces are generally of the slag-tapping variety, like their other European counterparts. Smithing, on the other hand, is carried out at ground-level until at least the sixteenth century in Ireland, whereas waist-level hearths become the norm further afield from the fourteenth century onwards. Ceramic tuyeres continue to be used as bellows protectors, whereas these are unknown elsewhere on the continent. Moreover, the lack of market centres at different times in late medieval Ireland, led to the appearance of isolated rural forges, a type of site unencountered in other European countries during that period. When these market centres are present, they appear to be the settings where bloom smithing is carried out. In summary, the research below not only offered us the opportunity to give late medieval ironworking the place it deserves in the broader knowledge of Ireland's past, but it also provided both a base for future research within the discipline, as well as a research model applicable to different time periods, geographical areas and, perhaps, different industries..

Time use, daily activities, and health-related quality of life of school-going late adolescents in Cork city and county: A cross-sectional study

Aim: This thesis examines a question posed by founding occupational scientist Dr. Elizabeth Yerxa (1993) – “what is the relationship between human engagement in a daily round of activity (such as work, play, rest and sleep) and the quality of life people experience including their healthfulness” (p. 3). Specifically, I consider Yerxa’s question in relation to the quotidian activities and health-related quality of life (HRQoL) of late adolescents (aged 15 - 19 years) in Ireland. This research enquiry was informed by an occupational perspective of health and by population health, ecological, and positive youth development perspectives. Methods: This thesis is comprised of five studies. Two scoping literature reviews informed the direction of three empirical studies. In the latter, cross-sectional time use and HRQoL data were collected from a representative sample of 731 school-going late adolescents (response rate 52%) across 28 schools across Cork city and county (response rate 76%). In addition to socio-demographic data, time use data were collected using a standard time diary instrument while a nationally and internationally validated instrument, the KIDSCREEN-52, was used to measure HRQoL. Variable-centred and person-centred analyses were used. Results: The scoping reviews identified the lack of research on well populations or an adolescent age range within occupational therapy and occupational science; limited research testing the popular assumption that time use is related to overall well-being and quality of life; and the absence of studies that examined adolescent 24-hour time use and quality of life. Established international trends were mirrored in the findings of the examination of weekday and weekend time use. Aggregate-level, variable-centred analyses yielded some significant associations between HRQoL and individual activities, independent of school year, school location, family context, social class, nationality or diary day. The person-centred analysis of overall time use identified three male profiles (productive, high leisure and all-rounder) and two female profiles (higher study/lower leisure and moderate study/higher leisure). There was tentative support for the association between higher HRQoL and more balanced time use profiles. Conclusion: The findings of this thesis highlight the gendered nature of adolescent time use and HRQoL. Participation in daily activities, singly and in combination, appears to be associated with HRQoL. However, the nature of this relationship is complex. Individually and collectively, adolescents need to be educated and supported to create health through their everyday patterns of doing.

GABRIEL URBAIN FAURÉ, THE UNSUNG MODERNIST: A PERFORMANCE SURVEY OF SELECTED LATE WORKS WRITTEN AFTER 1892 FOR PIANO SOLO, AND PIANO IN COLLABORATION WITH VIOLIN, VIOLONCELLO, AND VOICE

Gabriel Urbain Fauré lived during one of the most exciting times in music history. Spanning a life of 79 years (1845-1924), he lived through the height of Romanticism and the experimental avant-garde techniques of the early 20th century. In Fauré's music, one can find traces of Chopin, Liszt, Mendelssohn, Debussy and Poulenc. One can even argue that Fauré presages Skryabin and Shostakovich. The late works of Gabriel Fauré, chiefly those composed after 1892, testify to the argument that Fauré holds an important position in the shift from tonal to atonal composition and should be counted among such transitional composers as Gustav Mahler, Claude Debussy, Erik Satie, Richard Strauss, and Ferruccio Busoni. Fauré's unique way of fashioning harmonic impetus of almost purely linear means, resulting in a synthesis of harmonic and melodic devices, led me to craft the term mélodoharmonique. This term refers to a contrapuntally motivated technique of composition, particularly in a secondary layer of musical texture, in which a component of harmonic progression (i.e. arpeggiation, broken chord, etc.) is fused with linear motivic or thematic development. This dissertation seeks to bring to public attention through exploration in lecture and recital format, certain works of Gabriel Fauré, written after 1892. The repertoire will be selected from works for solo piano and piano in collaboration with violin, violoncello, and voice, which support the notion of Fauré as a modernist deserving larger recognition for his influence in the transition to atonal music. The recital repertoire includes the following--Song Cycles: La bonne chanson, opus 61; La chanson d'Ève, opus 95; Le jardin clos, opus 106; Mirages, opus 113; L'horizon chimérique, opus 118; Piano Works: Prelude in G minor opus 103, No. 3; Prelude in E minor opus 103, No. 9; Eleventh Nocturne, opus 104, No.1; Thirteenth Nocturne, opus 119; Chamber Works: Second Violin Sonata, opus 108; First Violoncello Sonata, opus 109; Second Violoncello Sonata, opus 117.

Hippocampus shape analysis and late-life depression.

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F(1,103) = 5.26; p = 0.0240) but not right hippocampus volume (F(1,103) = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms.

Genome-wide scan of copy number variation in late-onset Alzheimer's disease.

Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence disease predisposition. These studies have confirmed the well-known APOE epsilon4 risk allele, identified a novel variant that influences disease risk within the APOE epsilon4 population, found a SNP that modifies the age of disease onset, as well as reported the first sex-linked susceptibility variant. Here we report a genome-wide scan of Alzheimer's disease in a set of 331 cases and 368 controls, extending analyses for the first time to include assessments of copy number variation. In this analysis, no new SNPs show genome-wide significance. We also screened for effects of copy number variation, and while nothing was significant, a duplication in CHRNA7 appears interesting enough to warrant further investigation.

North atlantic deepwater temperature change during late pliocene and late quaternary climatic cycles

Variations in the ratio of magnesium to calcium (Mg/Ca) in fossil ostracodes from Deep Sea Drilling Project Site 607 in the deep North Atlantic show that the change in bottom water temperature during late Pliocene 41,000-year obliquity cycles averaged 1.5°C between 3.2 and 2.8 million years ago (Ma) and increased to 2.3°C between 2.8 and 2.3 Ma, coincidentally with the intensification of Northern Hemisphere glaciation. During the last two 100,000-year glacial-to-interglacial climatic cycles of the Quaternary, bottom water temperatures changed by 4.5°C. These results show that glacial deepwater cooling has intensified since 3.2 Ma, most likely as the result of progressively diminished deep-water production in the North Atlantic and of the greater influence of Antarctic bottom water in the North Atlantic during glacial periods. The ostracode Mg/Ca data also allow the direct determination of the temperature component of the benthic foraminiferal oxygen isotope record from Site 607, as well as derivation of a hypothetical sea-level curve for the late Pliocene and late Quaternary. The effects of dissolution on the Mg/Ca ratios of ostracode shells appear to have been minimal.

CONSERVATIVE AND PROGFESSIVE ASPECTS OF THE SONATA FROM LATE BEETHOVEN TO PROKOFIEV

The term 'sonata' arose in the early seventeenth-century Baroque period and was originally used to distinguish instrumental (sonata) music from vocal music. Later. the sonata style, as a reliable yet flexible compositional framework, was extensively shaped and utilized throughout the Classical period. Subsequently, in the Romantic period, freer creative, individualistic. and expressive musical elements began to be preferred by composers in their use of harmonj., tone color, form, and rhythm. However, even during the revolutionary Romantic period in music. the compositions which did not have a pre-defined format (character pieces, etc) were often comfortably framed and limited within the recognizable boundaries provided by the Classical sonata style. The sonata format, when used as a tool in musical composition, provides logical boundaries that may serve to organize any unexpected emotional expressions on the part of the composer. Yet the sonata framework is also flexible enough to allow freedom of expression. In the Romantic period and beyond, composers had relied, some more than others, upon the sonata's adaptable blend of stability and flexibility. In my opinion, it is more persuasive to express oneself musically within the framework of an established musical style. Thus, I have chosen my dissertation topic as the performance of six pieces incorporating elements of the reliable and flexible sonata style. The sonata of each composer that I have selected clearly demonstrates a tension between logic and emotion expressed within the sonata framework. However, the compositions can be divided interestingly into two groups, such as 'conservative' and 'progressive' group. The 'conservative' group consists of composers who seemed to strive for greater freedom of self-expression within the constraints of the traditional sonata form. On the other hand, the 'progressive' group consists of composers who seemed more to rely upon the sonata form to rein in and add stability to their highly individual and emotional musical ideas. It is my hope that this project will provide a stimulating viewpoint from which to consider the evolution and utilization of the sonata style especially as it is applied to the composition and performance of these six diverse and interesting pieces.

Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.

Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint.

No association between TGFB1 polymorphisms and late radiotherapy toxicity: a meta-analysis.

BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial. METHODS: We searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue. RESULTS: We finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size. CONCLUSIONS: This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study.

Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.

Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE.

Traumatic brain injury (TBI) has been increasingly accepted as a major external risk factor for neurodegenerative morbidity and mortality. Recent evidence indicates that the resultant chronic neurobiological sequelae following head trauma may, at least in part, contribute to a pathologically distinct disease known as Chronic Traumatic Encephalopathy (CTE). The clinical manifestation of CTE is variable, but the symptoms of this progressive disease include impaired memory and cognition, affective disorders (i.e., impulsivity, aggression, depression, suicidality, etc.), and diminished motor control. Notably, mounting evidence suggests that the pathology contributing to CTE may be caused by repetitive exposure to subconcussive hits to the head, even in those with no history of a clinically evident head injury. Given the millions of athletes and military personnel with potential exposure to repetitive subconcussive insults and TBI, CTE represents an important public health issue. However, the incidence rates and pathological mechanisms are still largely unknown, primarily due to the fact that there is no in vivo diagnostic tool. The primary objective of this manuscript is to address this limitation and discuss potential neuroimaging modalities that may be capable of diagnosing CTE in vivo through the detection of tau and other known pathological features. Additionally, we will discuss the challenges of TBI research, outline the known pathology of CTE (with an emphasis on Tau), review current neuroimaging modalities to assess the potential routes for in vivo diagnosis, and discuss the future directions of CTE research.