To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.
Neutrophil–lymphocyte ratio has been associated with clinical outcomes in several groups of cardiac patients, including patients with coronary artery disease, cardiac failure, and cardiac transplant recipients. We hypothesised that pre- and/or post-operative haematological cell counts are associated with clinical outcomes in children undergoing cardiac surgery for CHD. We performed a post hoc analysis of data collected as part of a prospective observational cohort study (n = 83, data available n = 47) of children evaluated for glucocorticoid receptor levels after cardiac surgery (July 2015–January 2016). The association of neutrophil–lymphocyte ratio with low cardiac output syndrome, time to inotrope free, and vasoactive-inotropic score was examined using proportional odds analysis, cox regression, and linear regression models, respectively. A majority (80%) of patients were infants (median/interquartile range 4.1/0.2–7.6 months) with conotruncal (36%) and left-sided obstructed lesions (28%). Two patients required mechanical circulatory support and three died. Higher pre-operative neutrophil–lymphocyte ratio was associated with higher cumulative odds of severe/moderate versus mild low cardiac output on post-operative day 1 (odds ratio 2.86; 95% confidence interval 1.18–6.93; p = 0.02). Pre-operative neutrophil–lymphocyte ratio was not significantly associated with time to inotrope free or vasoactive-inotrope score. Post-operative neutrophil–lymphocyte ratio was also not associated with outcomes. In children after congenital heart surgery, higher pre-operative neutrophil–lymphocyte ratio was associated with a higher chance of low cardiac output in the early post-operative period. Pre-operative neutrophil–lymphocyte ratio maybe a useful prognostic marker in children undergoing congenital heart surgery.
To investigate the spatial distribution of self-harm incidence rates, their socioeconomic correlates and sex/age differences using data on self-harm presentations to emergency departments from The Manchester Self-Harm Project (2003–2013).
Smoothed standardised incidence ratios for index self-harm episodes (n = 14 771) and their associations with area-level socioeconomic factors across 258 small areas (median population size = 1470) in the City of Manchester municipality were estimated using Bayesian hierarchical models.
Higher numbers and rates of self-harm were found in the north, east and far southern zones of the city, in contrast to below average rates in the city centre and the inner city zone to the south of the centre. Males and females aged 10–24, 25–44 and 45–64 years showed similar geographical patterning of self-harm. In contrast, there was no clear pattern in the group aged 65 years and older. Fully adjusted analyses showed a positive association of self-harm rates with the percentage of the unemployed population, households privately renting, population with limiting long-term illness and lone-parent households, and a negative association with the percentage of ethnicity other than White British and travel distance to the nearest hospital emergency department. The area-level characteristics investigated explained a large proportion (four-fifths) of the variability in area self-harm rates. Most associations were restricted to those aged under 65 years and some associations (e.g. with unemployment) were present only in the youngest age group.
The findings have implications for allocating prevention and intervention resources targeted at high-risk groups in high incidence areas. Targets for area-based interventions might include tackling the causes and consequences of joblessness, better treatment of long-term illness and consideration of the accessibility of health services.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Objectives: Patients with body dysmorphic disorder (BDD) have difficulty in recognising facial emotions, and there is evidence to suggest that there is a specific deficit in identifying negative facial emotions, such as sadness and anger. Methods: This study investigated facial emotion recognition in 19 individuals with BDD compared with 21 healthy control participants who completed a facial emotion recognition task, in which they were asked to identify emotional expressions portrayed in neutral, happy, sad, fearful, or angry faces. Results: Compared to the healthy control participants, the BDD patients were generally less accurate in identifying all facial emotions but showed specific deficits for negative emotions. The BDD group made significantly more errors when identifying neutral, angry, and sad faces than healthy controls; and were significantly slower at identifying neutral, angry, and happy faces. Conclusions: These findings add to previous face-processing literature in BDD, suggesting deficits in identifying negative facial emotions. There are treatment implications as future interventions would do well to target such deficits.
OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.
The kink-turn (k-turn) is a widespread structural motif found in functional RNA species. It typically comprises a three-nucleotide bulge followed by tandem trans sugar edge-Hoogsteen G:A base pairs. It introduces a sharp kink into the axis of duplex RNA, juxtaposing the minor grooves. Cross-strand H-bonds form at the interface, accepted by the conserved adenine nucleobases of the G:A basepairs. Alternative acceptors for one of these divides the k-turns into two conformational classes N3 and N1. The base pair that follows the G:A pairs (3b:3n) determines which conformation is adopted by a given k-turn. k-turns often mediate tertiary contacts in folded RNA species and frequently bind proteins. Common k-turn binding proteins include members of the L7Ae family, such as the human 15·5k protein. A recognition helix within these proteins binds in the widened major groove on the outside of the k-turn, that makes specific H-bonds with the conserved guanine nucleobases of the G:A pairs. L7Ae binds with extremely high affinity, and single-molecule data are consistent with folding by conformational selection. The standard, simple k-turn can be elaborated in a variety of ways, that include the complex k-turns and the k-junctions. In free solution in the absence of added metal ions or protein k-turns do not adopt the tightly-kinked conformation. They undergo folding by the binding of proteins, by the formation of tertiary contacts, and some (but not all) will fold on the addition of metal ions. Whether or not folding occurs in the presence of metal ions depends on local sequence, including the 3b:3n position, and the −1b:−1n position (5′ to the bulge). In most cases −1b:−1n = C:G, so that the 3b:3n position is critical since it determines both folding properties and conformation. In general, the selection of these sequence matches a given k-turn to its biological requirements. The k-turn structure is now very well understood, to the point at which they can be used as a building block for the formation of RNA nano-objects, including triangles and squares.
OBJECTIVES/SPECIFIC AIMS: (1) Evaluate safety of a novel influenza vaccination strategy in patients with plasma cell disorders. (2) Measure laboratory-confirmed influenza infection rates following a novel influenza vaccination strategy in patients with plasma cell disorders. (3) Evaluate clinical correlates of response following a novel influenza vaccination strategy in patients with plasma cell disorders. METHODS/STUDY POPULATION: We conducted a double-blind, randomized study over the 2015–16 flu season, comparing 2 doses of Fluzone® High-Dose influenza vaccination (separated by 30 d) to the current standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio compared with standard of care arm. Standard of care influenza vaccination was considered single age-based vaccination (standard dose for those <65 y and high dosefor those ≥65 y) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a PCD and no contraindication to trivalent inactivated influenza vaccine. The primary endpoint was laboratory-confirmed flu infection rate. Protocol-driven surveillance screened patients for flu-like illnesses and performed laboratory testing for influenza until the end of the flu season in May 2016. Secondary endpoints include HAI titer serologic response rates, clinical correlates of protection from influenza infection, and exploratory studies of cell-mediated immunity through characterization of T cell subpopulations, cytokine profiles, and flu-specific T-cell responsiveness. RESULTS/ANTICIPATED RESULTS: In total, 122 plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Of those 48 patients received a single standard of care influenza vaccination and 74 patients received 2 doses of Fluzone® high-dose vaccine. Median age was 67 years (range 42–90). This 2-dose vaccination strategy was safely tolerated in all patients with no grade 2 adverse events attributed to vaccine. With close clinical follow-up, only 4% of patients receiving 2 vaccine doses developed laboratory confirmed influenza Versus 8.3% of those receiving single vaccine. When compared to the expected CDC influenza infection rate of 10%–15%, 1 sample, 2-tailed binomial testing revealed patients receiving 2 vaccines experienced a significantly lower rate of infection than the expected rate (p<0.05) whereas those receiving single vaccine showed no significant difference (p=0.38). DISCUSSION/SIGNIFICANCE OF IMPACT: This randomized study demonstrates that the 2 dose strategy of Fluzone® high-dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with significantly less than expected laboratory-confirmed influenza infections. The results suggest that this novel vaccination strategy may have a clinical benefit in reducing influenza infections in plasma cell disorder patients and thus may have practice changing implications. Final analyses of serologic responses, clinical correlates of response, and cell-mediated immune correlates may provide valuable insights into in vivo “immune-competence” in patients with plasma cell disorders.
The Yellow Sea region is of high global importance for waterbird populations, but recent systematic bird count data enabling identification of the most important sites are relatively sparse for some areas. Surveys of waterbirds at three sites on the coast of southern Jiangsu Province, China, in 2014 and 2015 produced peak counts of international importance for 24 species, including seven globally threatened and six Near Threatened species. The area is of particular global importance for the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea (peak count across all three study sites: 62 in spring  and 225 in autumn  and ‘Endangered’ Spotted Greenshank Tringa guttifer (peak count across all three study sites: 210 in spring  and 1,110 in autumn ). The southern Jiangsu coast is therefore currently the most important migratory stopover area in the world, in both spring and autumn, for both species. Several serious and acute threats to waterbirds were recorded at these study sites. Paramount is the threat of large-scale land claim which would completely destroy intertidal mudflats of critical importance to waterbirds. Degradation of intertidal mudflat habitats through the spread of invasive Spartina, and mortality of waterbirds by entrapment in nets or deliberate poisoning are also real and present serious threats here. Collisions with, and displacement by, wind turbines and other structures, and industrial chemical pollution may represent additional potential threats. We recommend the rapid establishment of effective protected areas for waterbirds in the study area, maintaining large areas of open intertidal mudflat, and the urgent removal of all serious threats currently faced by waterbirds here.
Objectives: Body dysmorphic disorder (BDD) is characterized by repetitive behaviors and/or mental acts occurring in response to preoccupations with perceived defects or flaws in physical appearance. There are some similarities, but also important differences, between BDD and obsessive-compulsive disorder (OCD), not just in terms of core clinical symptoms, but possibly in the domain of perception. This study compared the nature and extent of perceptual anomalies in BDD versus OCD and health controls (HC), using a modified Mooney task. Methods: We included 21 BDD, 19 OCD, and 21 HC participants, who were age-, sex-, and IQ-matched. A set of 40 Mooney faces and 40 Mooney objects arranged in three configurations (i.e., upright, inverted, or scrambled) were presented under brief (i.e., 500 ms) free-viewing conditions. Participants were asked to decide whether each image represented a human face, an object, or neither in a forced-choice paradigm. Results: The BDD group showed significantly reduced face and object inversion effects relative to the other two groups. This was accounted for by BDD participants being significantly more accurate in identifying inverted Mooney faces and objects than the other participants. Conclusions: These data were interpreted as reflecting an overreliance on independent components at the expense of holistic (configural) processing in BDD. (JINS, 2017, 23, 471–480)
To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients.
Multicenter, matched case-control study.
Four LTACHs in Chicago, Illinois.
Each case patient included in this study had a KPC-negative rectal surveillance culture on admission followed by a KPC-positive surveillance culture later in the hospital stay. Each matched control patient had a KPC-negative rectal surveillance culture on admission and no KPC isolated during the hospital stay.
From June 2012 to June 2013, 2,575 patients were admitted to 4 LTACHs; 217 of 2,144 KPC-negative patients (10.1%) acquired KPC. In total, 100 of these patients were selected at random and matched to 100 controls by LTACH facility, admission date, and censored length of stay. Acquisitions occurred a median of 16.5 days after admission. On multivariate analysis, we found that exposure to higher colonization pressure (OR, 1.02; 95% CI, 1.01–1.04; P=.002), exposure to a carbapenem (OR, 2.25; 95% CI, 1.06–4.77; P=.04), and higher Charlson comorbidity index (OR, 1.14; 95% CI, 1.01–1.29; P=.04) were independent risk factors for KPC acquisition; the odds of KPC acquisition increased by 2% for each 1% increase in colonization pressure.
Higher colonization pressure, exposure to carbapenems, and a higher Charlson comorbidity index independently increased the odds of KPC acquisition among LTACH patients. Reducing colonization pressure (through separation of KPC-positive patients from KPC-negative patients using strict cohorts or private rooms) and reducing carbapenem exposure may prevent KPC cross transmission in this high-risk patient population.
We aimed to explore whether a) step stool use is associated with improved cardiopulmonary resuscitation (CPR) quality; b) provider adjusted height is associated with improved CPR quality; and if associations exist, c) determine whether just-in-time (JIT) CPR training and/or CPR visual feedback attenuates the effect of height and/or step stool use on CPR quality.
We analysed data from a trial of simulated cardiac arrests with three study arms: No intervention; CPR visual feedback; and JIT CPR training. Step stool use was voluntary. We explored the association between 1) step stool use and CPR quality, and 2) provider adjusted height and CPR quality. Adjusted height was defined as provider height + 23 cm (if step stool was used). Below-average height participants were ≤ gender-specific average height; the remainder were above average height. We assessed for interaction between study arm and both adjusted height and step stool use.
One hundred twenty-four subjects participated; 1,230 30-second epochs of CPR were analysed. Step stool use was associated with improved compression depth in below-average (female, p=0.007; male, p<0.001) and above-average (female, p=0.001; male, p<0.001) height providers. There is an association between adjusted height and compression depth (p<0.001). Visual feedback attenuated the effect of height (p=0.025) on compression depth; JIT training did not (p=0.918). Visual feedback and JIT training attenuated the effect of step stool use (p<0.001) on compression depth.
Step stool use is associated with improved compression depth regardless of height. Increased provider height is associated with improved compression depth, with visual feedback attenuating the effects of height and step stool use.
Lithium sulfur (Li–S) batteries have the potential to provide higher energy storage density at lower cost than conventional lithium ion batteries. A key challenge for Li–S batteries is the loss of sulfur to the electrolyte during cycling. This loss can be mitigated by sequestering the sulfur in nanostructured carbon–sulfur composites. The nanoscale characterization of the sulfur distribution within these complex nanostructured electrodes is normally performed by electron microscopy, but sulfur sublimates and redistributes in the high-vacuum conditions of conventional electron microscopes. The resulting sublimation artifacts render characterization of sulfur in conventional electron microscopes problematic and unreliable. Here, we demonstrate two techniques, cryogenic transmission electron microscopy (cryo-TEM) and scanning electron microscopy in air (airSEM), that enable the reliable characterization of sulfur across multiple length scales by suppressing sulfur sublimation. We use cryo-TEM and airSEM to examine carbon–sulfur composites synthesized for use as Li–S battery cathodes, noting several cases where the commonly employed sulfur melt infusion method is highly inefficient at infiltrating sulfur into porous carbon hosts.
Heart failure (HF) is a major public health problem worldwide and in Asia. Sacubitril/valsartan reduces cardiovascular death and hospitalizations for HF. However, decision makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of current standard of care.
Using a Markov model, we projected lifetime clinical and economic outcomes of sacubitril/valsartan versus enalapril for 66-year-old patients with HF in Singapore. Key health states included New York Heart Association (NYHA) classes; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Probabilities of events were based on the PARADIGM-HF trial. The uncertain treatment effect of sacubtril/valsartan in Asian patients was modelled using a hazard ratio (HR) of 1 as upper limit in sensitivity analyses. Utilities were obtained from published literature. Local national epidemiological and cost data were applied. Analyses were conducted from the Singapore healthcare payer's perspective. Both one-way and Probabilistic Sensitivity Analyses (PSA) based on 10,000 Monte Carlo simulations were performed.
Compared to enalapril, sacubitril/valsartan was associated with an incremental cost-effectiveness ratio (ICER) of SGD74k (USD52k) per quality-adjusted life year (QALY) gained. The cost-effectiveness of sacubitril/valsartan was highly dependent on its effectiveness in reducing the risk of cardiovascular death. However, this was uncertain, particularly in the Asian subgroup, where results were not statistically significant. In sensitivity analyses using results from Asian patients, the ICERs ranged from SGD41k (USD30k) to SGD1.3 million (USD 0.94 million) per QALY gained. PSA showed the probability of sacubitril/valsartan being cost-effective was below 1 percent, 12 percent and 71 percent at thresholds of SGD20k (USD14k), SGD50k (USD36k) and SGD100k (USD 72k) per QALY gained, respectively.
Given the uncertain ICER, sacubtril/valsartan may not provide good value for money compared to enalapril in reducing cardiovascular morbidity and mortality in patients with HF at the current daily cost. Our study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering HF therapy.
Mesoporous titania films are prepared via the polymer-template assisted sol-gel synthesis at low temperatures, using the titania precursor ethylene glycol-modified titanate (EGMT) and the diblock copolymer polystyrene-block-polyethyleneoxide (PS-b-PEO). UV-irradiation is chosen as a low temperature technique to remove the polymer template and thereby to obtain titania sponge-like nanostructures at processing temperatures below 100 °C. After different UV irradiation times, ranging for 0 h to 24 h, the surface and inner morphologies of the titania films are studied with scanning electron microscopy (SEM) and grazing incidence small-angle x-ray scattering (GISAXS), respectively. The evolution of the band gap energies is investigated using ultraviolet/visible (UV/Vis) spectroscopy. The findings reveal that 12 h UV-treatment is sufficient to remove the polymer template from the titania/PS-b-PEO composite films with a thickness of 80 nm, and the determined bad gap energies indicate an incomplete crystallization of the titania nanostructures.
Alnico alloys have long been used as strong permanent magnets because of their ferromagnetism and high coercivity. Understanding their structural details allows for better prediction of the resulting magnetic properties. However, quantitative three-dimensional characterization of the phase separation in these alloys is still challenged by the spatial quantification of nanoscale phases. Herein, we apply a dual tomography approach, where correlative scanning transmission electron microscopy (STEM) energy-dispersive X-ray spectroscopic (EDS) tomography and atom probe tomography (APT) are used to investigate the initial phase separation process of an alnico 8 alloy upon non-magnetic annealing. STEM-EDS tomography provides information on the morphology and volume fractions of Fe–Co-rich and Νi–Al-rich phases after spinodal decomposition in addition to quantitative information of the composition of a nanoscale volume. Subsequent analysis of a portion of the same specimen by APT offers quantitative chemical information of each phase at the sub-nanometer scale. Furthermore, APT reveals small, 2–4 nm Fe-rich α1 phases that are nucleated in the Ni-rich α2 matrix. From this information, we show that phase separation of the alnico 8 alloy consists of both spinodal decomposition and nucleation and growth processes. The complementary benefits and challenges associated with correlative STEM-EDS and APT are discussed.
We demonstrate that the second-Stokes output from a diamond Raman laser, pumped by a femtosecond Ti:Sapphire laser, can be used to efficiently excite red-emitting dyes by two-photon excitation at 1,080 nm and beyond. We image HeLa cells expressing red fluorescent protein, as well as dyes such as Texas Red and Mitotracker Red. We demonstrate the potential for simultaneous two-color, two-photon imaging with this laser by using the residual pump beam for excitation of a green-emitting dye. We demonstrate this for the combination of Alexa Fluor 488 and Alexa Fluor 568. Because the Raman laser extends the wavelength range of the Ti:Sapphire laser, resulting in a laser system tunable to 680–1,200 nm, it can be used for two-photon excitation of a large variety and combination of dyes.