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A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Photonic crystal surfaces represent a class of resonant optical structures that are capable of supporting high intensity electromagnetic standing waves with near-field and far-field properties that can be exploited for high sensitivity detection of biomolecules and cells. While modulation of the resonant wavelength of a photonic crystal by the dielectric permittivity of adsorbed biomaterials enables label-free detection, the resonance can also be tuned to coincide with the excitation wavelength of common fluorescent tags - including organic molecules and semiconductor quantum dots. Photonic crystals are also capable of efficiently channeling fluorescent emission into a preferred direction for enhanced extraction efficiency. Photonic crystals can be designed to support multiple resonant modes that can perform label free detection, enhanced fluorescence excitation, and enhanced fluorescence extraction simultaneously on the same device. Because photonic crystal surfaces may be inexpensively produced over large surface areas by nanoreplica molding processes, they can be incorporated into disposable labware for applications such as pharmaceutical high throughput screening. In this talk, the optical properties of surface photonic crystals will be reviewed and several applications will be described, including results from screening a 200,000-member chemical compound library for inhibitors of protein-DNA interactions, gene expression microarrays, and high sensitivity of protein biomarkers.
High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
To investigate the extent of suspected hybridization between the brolga Antigone rubicunda and the Australian sarus crane Antigone antigone gillae, first noted in the 1970s, we analysed the genetic diversity of 389 feathers collected from breeding and flocking areas in north Queensland, Australia. We compared these with 15 samples from birds of known identity, or that were phenotypically typical. Bayesian clustering based on 10 microsatellite loci identified nine admixed birds, confirming that Australian cranes hybridize in the wild. Four of these were backcrosses, also confirming that wild Australian crane hybrids are fertile. Genetic analyses identified 10 times more hybrids than our accompanying visual field observations. Our analyses also provide the first definitive evidence that both brolgas and sarus cranes migrate between the Gulf Plains, the principal breeding area for sarus cranes, and major non-breeding locations on the Atherton Tablelands. We suggest that genetic analysis of shed feathers could potentially offer a cost-effective means to provide ongoing monitoring of this migration. The first observations of hybrids coincided with significantly increased opportunities for interaction between the two species when foraging on agricultural crops, which have developed significantly in the Atherton Tablelands flocking area since the 1960s. As the sarus crane is declining in much of its Asian range, challenges to the genetic integrity of the Australian sarus crane populations have international conservation significance.
Alzheimer's disease and vascular dementia are associated with overlapping symptoms of anxiety and depression. More accurate discrimination between emerging neuropsychiatric and cognitive symptoms would better assist illness detection. The potential for protection against cognitive decline and dementia following early identification and intervention of neuropsychiatric symptoms warrants investigation.
Declaration of interest
B.J.S. consults for Peak, Mundipharma and Cambridge Cognition. J.T.O. has acted as a consultant for TauRx, Axon, GE Healthcare and Lilly.
Percutaneous tunneled drainage catheter (PTDC) placement is a palliative alternative to serial paracenteses in patients with end-stage cancer and refractory ascites. The impact of PTDC on quality of life (QoL) and long-term outcomes has not been prospectively described. The objective was to evaluate changes in QoL after PTDC.
Eligible adult patients with end-stage cancer undergoing PTDC placement for refractory ascites completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and McGill Quality of Life instruments before PTDC placement and at 2 to 7 days and 2 to 4 weeks after PTDC. Catheter function, complications, and laboratory values were assessed. Analysis of QoL data was evaluated with a stratified Wilcoxon signed-rank test.
Fifty patients enrolled. Survey completion ranged from 65% to 100% (median 88%) across timepoints. All patients had a Tenckhoff catheter, with 98% technical success. Median survival after PTDC was 38 days (95% confidence interval = 32, 57 days). European Organization for Research and Treatment of Cancer scores showed improvement in global QoL (p = 0.03) at 1 week postprocedure (PP). Significant symptom improvement was reported for fatigue, nausea/vomiting, pain, dyspnea, insomnia, and appetite at 1 week PP and was sustained at 3 weeks PP for dyspnea (p < 0.01), insomnia (p < 0.01), and appetite loss (p = 0.03). McGill Quality of Life demonstrated overall QoL improvement at 1 (p = 0.03) and 3 weeks (p = 0.04) PP. Decline in sodium and albumin values pre- and post-PTDC slowed significantly (albumin slope –0.43 to –0.26, p = 0.055; sodium slope –2.50 to 1.31, p = 0.04). Creatinine values increased at an accelerated pace post-PTDC (0.040 to 0.21, p < 0.01). Thirty-eight catheter-related complications occurred in 24 of 45 patients (53%).
Significance of results
QoL and symptoms improved after PTDC placement for refractory ascites in patients with end-stage malignancy. Decline in sodium and albumin values slowed postplacement. This study supports the use of a PTDC for palliation of refractory ascites in cancer patients.
Hospice nurses frequently encounter patients and families under tremendous emotional distress, yet the communication techniques they use in emotionally charged situations have rarely been investigated. In this study, researchers sought to examine hospice nurses’ use of validation communication techniques, which have been shown in prior research to be effective in supporting individuals experiencing emotional distress.
Researchers performed a directed content analysis of audiorecordings of 65 hospice nurses’ home visits by identifying instances when nurses used validation communication techniques and rating the level of complexity of those techniques.
All nurses used validation communication techniques at least once during their home visits. Use of lower level (i.e., more basic) techniques was more common than use of higher level (i.e., more complex) techniques.
Significance of Results
Although hospice nurses appear to use basic validation techniques naturally, benefit may be found in the use of higher level techniques, which have been shown to result in improved clinical outcomes in other settings.
Porotectosilicates are a class of siliceous crystalline materials which includes both zeolites and materials which resemble zeolites in crystal structure, but may or may not have ion exchange capability. The framework structures of these porotectosilicates are comprised of “T” atoms tetrahedrally coordinated to oxygen, where “T” can be Al, Si or any other element capable of isomorphous substitution for silicon. The occurrence of small crystals and the additional problems introduced by the presence of stacking faults and crystal twinning make structure determination of porotectosilicates by conventional approaches difficult.
The industrial significance of these materials has led to the development of a technique which permits the determination of their structure. The method involves the construction of appropriate hypothetical models, a DLS refinement followed by computation of a Smith plot for comparison with the experimental powder pattern. Model crystal structures may now be refined using the Rietveld technique. It is expected that this technique will contribute significantly to the solution of porotectosilicate structures which are difficult--if not impossible--to establish by other techniques.
X-ray diffraction angles are measured precisely, conveniently, and automatically by a specially designed instrument, the automatic precision X-ray goniometer connected on line to an Elliott 903B data processor. A monitor program controls two such instruments and two diffractometers simultaneously and allows a comprehensive set of experiments to be performed. The sensitivity is such that, when translated into terms of changes in the crystal-lattice parameter, a precision of 1 part in 10,000,000 is being attained, and indications are that absolute measurements are almost as good. The procedures, instrument, and automatic control are described, and the results of performance tests and some applications are given.
The forces on an object impacting the water are extreme in the early moments of water entry and can cause structural damage to biological and man-made bodies alike. These early-time forces arise largely from added mass, peaking when the submergence is much less than one body length. We experimentally investigate a means of reducing impact forces on a rigid sphere by placing the sphere inside a jet of water so that the jet strikes the quiescent water surface prior to entry of the sphere into the pool. The water jet accelerates the pool liquid and forms a cavity into which a sphere falls. Through on-board accelerometer measurements and high-speed imaging, we quantify the force reduction compared to the case of a sphere entering a quiescent pool. Finally, we find the emergence of a critical jet volume required to maximize force reduction; the critical volume is rationalized using scaling arguments informed by near-surface particle image velocimetry (PIV) data.
This paper explores thin films of the entropy-stabilized oxide (ESO) composition MgxNixCoxCuxZnxScxO (x ~ 0.167) grown by laser ablation in incremental gas pressures and O2/Ar ratios to modulate particle kinetic energy and plume reactivity. Low pressures supporting high kinetic energy adatoms favor the kinetic stabilization of a single rocksalt phase, while high pressures (low kinetic energy adatoms) result in phase separation. The pressure threshold for phase separation is a function of O2/Ar ratio. These findings suggest large kinetic energies facilitate the assembly and quench of metastable ESO phases that may require immoderate physical or chemical conditions to synthesize using near-equilibrium techniques.
OBJECTIVES/SPECIFIC AIMS: Gliomas are the most lethal and common
primary tumor type in the central nervous system across all age groups; affected
adults have a life expectancy of just 14 months. As glioma cells invade the
surrounding normal parenchyma they remodel the composition and ultrastructure of
the surrounding extracellular matrix (ECM), suggesting that the native (i.e.,
“normal”) microenvironment is not ideal for their survival
and proliferation. Recent reports describe suppressive and/or lethal
effects of mammalian ECM hydrogels derived from normal (nonneoplastic) sources
upon various cancer types. ECM-based bioscaffolds placed at sites of neoplastic
tissue resection in humans have never been reported to facilitate cancer
recurrence. The objective of the present research is to evaluate mammalian ECM
as a novel approach to glioma therapy. METHODS/STUDY POPULATION: ECM
hydrogels from porcine dermis, small intestine, and urinary bladder were
produced as described previously. Primary glioma cells were graciously supplied
by Drs. Nduka Amankulor and Johnathan Engh, and U-87 MG were ordered through
ATCC. Cells were plated onto tissue culture plastic at
~60% confluence and allowed to attach for 24 hours before
treatment. The saline-soluble fraction (SSF) of ECM was obtained by mixing
lyophilized, comminuted ECM with 0.9% saline for 24 hours then
filtering the resulting mixture through a 10 kDa molecular weight cutoff column.
All assays and kits were followed according to the manufacturer’s
instructions. Cell viability was measured via MTT assay
(Vybrant® MTT Cell Proliferation Assay, Invitrogen)
and by live/dead staining
(LIVE/DEAD® Cell Imaging Kit, Invitrogen). Time
lapse videos were created by taking images every 20 minutes for 18 hours
(phase-contrast) or every 10 minutes for 12 hours (darkfield). NucView reagent
was ordered from Biotium. Temozolomide was ordered through Abmole. All in vivo
work was conducted according to protocols approved by the University of
Pittsburgh’s IACUC office. RESULTS/ANTICIPATED RESULTS:
ECM hydrogels derived from porcine dermis, small intestine, or urinary bladder
all decreased the viability of primary glioma cells in vitro, with urinary
bladder extracellular matrix (UBM) having the most dramatic effects. The SSF of
UBM (UBM-SSF), devoid of the fibrillar, macromolecular components of ECM, was
sufficient to recapitulate this detrimental effect upon neoplastic cells in
vitro and was used for the remainder of the experiments described herein. In a
cell viability assay normalized to the media treatment, non-neoplastic CHME5 and
N1E-115 cells scored 103% and 114% after 48 hours when
treated with UBM-SSF and 2 primary high-grade glioma cell types scored
17% and 30.5% with UBM-SSF (n=2).
Phase-contrast time-lapse video showed CHME5 and HFF thriving in the presence of
UBM-SSF for 18 hours while most primary glioma cells shriveled and died within
this time. Darkfield time-lapse video of wells containing Nucview dye,
fluorescent upon cleavage by active caspase-3, confirmed that within 12 hours
most primary glioma cells underwent apoptosis while CHME5 and HFF did not. In
culture with primary astrocytes, high grade primary glioma cells, and U-87 MG
glioma cells for 24 hours, UBM-SSF was found to significantly increase the
population of primary astrocytes compared with media
(p<0.05) while decreasing the 2 glioma cell types to
approximately one-third as many cells as the media control
(p<0.0001). A dose-response of temozolomide from 0
to 10,000 μM showed that when treating 2 non-neoplastic cell types
(CHME5 and HFF) and 2 types of primary glioma cell there was no difference in
survivability at any concentration. Contrasted to this, a dose-response of
UBM-SSF from 350 to 7000 μg/mL showed that the
non-neoplastic cells survived significantly better than the glioma cells at
concentrations of 875 μg/mL and upward
(p<0.05). In preliminary animal experiments, large
primary glioma tumors in the flanks of athymic nude mice were resected and
replaced with either UBM SSF or Matrigel (an ECM product of neoplastic cell
origin). After 7 days the resection sites with UBM-SSF had little tumor regrowth
if any compared with the dramatic recurrence seen in the Matrigel injection
sites (n=2). In a separate survival study comparing PBS to UBM-SSF
injections in the flank-resection model, all animals given PBS had to be
sacrificed at 9, 11, and 11 days (n=3) whereas animals given UBM-SSF
were sacrificed at 15, 24, and 39 days (n=3), indicating a moderate
increase in survival due to the UBM-SSF. DISCUSSION/SIGNIFICANCE OF
IMPACT: Since the introduction of the pan-cytotoxic chemotherapeutic agent TMZ
in 2005, the standard of care for patients with glioblastoma multiforme has not
improved. These findings indicate that non-neoplastic ECM contains potent
bioactive regulators capable of abrogating malignancy. Our in vitro data suggest
these molecules appear to have no deleterious effect on non-neoplastic cells
while specifically inducing apoptosis in glioma cells. Our in vivo data suggest
that these molecules may be useful in delaying glioma recurrence, thus resulting
in extended lifespan. Delivering soluble fractions of ECM to a tumor site may
represent a novel approach to glioma therapy, sidestepping traditional cytotoxic
therapies in favor of utilizing putative endogenous anti-tumor pathways.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
In the Western world, a significant portion of college students have gambled. College gamblers have one of the highest rates of problem gambling. To date, there have been no studies on gambling participation or the rates of problem gambling in India.
This study evaluated the prevalence of gambling participation and problem gambling in college students in India. It also evaluated demographic and psychosocial correlates of gambling in that population.
We surveyed 5784 college students from 58 colleges in the district of Ernakulam, Kerala, India, using cluster random sampling. Students completed questionnaires that addressed gambling, substance use, psychological distress, suicidality and attention-deficit hyperactivity disorder (ADHD).
A total of 5580 completed questionnaires were returned, and while only 1090 (19.5%) college students reported having ever gambled, 415 (7.4%) reported problem gambling. Lotteries were the most popular form of gambling. Problem gamblers in comparison with non-gamblers were significantly more likely to be male, have a part-time job, greater academic failures, higher substance use, higher psychological distress scores, higher suicidality and higher ADHD symptom scores. In comparison with non-problem gamblers, problem gamblers were significantly more likely to have greater academic failures, higher psychological distress scores, higher suicidality and higher ADHD symptom scores.
This study, the first to look at the prevalence of gambling in India, found relatively low rates of gambling participation in college students but high rates of problem gambling among those who did gamble. Correlates of gambling were generally similar to those noted in other countries. Since 38% of college students who had gambled had a gambling problem, there is a need for immediate public health measures to raise awareness about gambling, and to prevent and treat problem gambling in this population.