Purpose
There is growing interest in low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case–control analysis, we compared the efficacy of LDMC and ...conventional chemotherapy (CCT) in MBC.
Methods
Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two controls who received CCT. Age, number of chemotherapy lines and metastatic sites as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate longer than 24 weeks (DCR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR) and subgroup analyses using the matching criteria.
Results
40 cases and 80 controls entered the study. 30.0% patients with LDMC and 22.5% patients with CCT showed DCR (
p
= 0.380). The median PFS was 12.0 weeks in both groups (
p
= 0.218) and the median DoR was 31.0 vs. 20.5 weeks (
p
= 0.383), respectively. Among younger patients, DCR was 40.0% in LDMC vs. 25.0% in the CCT group (
p
= 0.249). DCR was achieved in 33.3% vs. 26.2% non-heavily pretreated patients (
p
= 0.568) and in 36.0% vs. 18.0% patients without multiple metastases (
p
= 0.096), respectively. In the HR-positive group, 30.0% LDMC vs. 28.3% CCT patients showed DCR (
p
= 1.000). Among triple-negative patients, DCR was achieved in 30.0% LDMC and 5.0% CCT patients (
p
= 0.095).
Conclusions
We demonstrated a similar efficacy of LDMC compared to CCT in the treatment of MBC. Thus, LDMC may be a valuable treatment option in selected MBC patients.
Ion trap in a semiconductor chip Stick, D; Hensinger, W. K; Olmschenk, S ...
Nature physics,
01/2006, Volume:
2, Issue:
1
Journal Article
Peer reviewed
Open access
The electromagnetic manipulation of isolated atoms has led to many advances in physics, from laser cooling and Bose-Einstein condensation of cold gases to the precise quantum control of individual ...atomic ions. Work on miniaturizing electromagnetic traps to the micrometre scale promises even higher levels of control and reliability. Compared with 'chip traps' for confining neutral atoms, ion traps with similar dimensions and power dissipation offer much higher confinement forces and allow unparalleled control at the single-atom level. Moreover, ion microtraps are of great interest in the development of miniature mass-spectrometer arrays, compact atomic clocks and, most notably, large-scale quantum information processors. Here we report the operation of a micrometre-scale ion trap, fabricated on a monolithic chip using semiconductor micro-electromechanical systems (MEMS) technology. We confine, laser cool and measure heating of a single 111Cd+ ion in an integrated radiofrequency trap etched from a doped gallium-arsenide heterostructure.
Abstract Background context Whereas the costs of primary surgery, revisions, and selected complications for adult spinal deformity (ASD) have been individually reported in the literature, the total ...costs over several years after surgery have not been assessed. The determinants of such costs are also not well understood in the literature. Purpose This study analyzes the total hospital costs and operating room (OR) costs of ASD surgery through extended follow-up. Study design/setting Single-center retrospective analysis of consecutive surgical patients. Patient sample Four hundred eighty-four consecutive patients undergoing surgical treatment for ASD from January 2005 through January 2011 with minimum three levels fused. Outcome measures Costs were collected from hospital administrative data on the total hospital costs incurred for the operation and any related readmissions, expressed in 2010 dollars and discounted at 3.5% per year. Detailed data on OR costs, including implants and biologics, were also collected. Methods We performed a series of paired t tests and Wilcoxon signed-rank tests for differences in total hospital costs over different follow-up periods. The goal of these tests was to identify a time period over which average costs plateau and remain relatively constant over time. Generalized linear model regression was used to estimate the effect of patient and surgical factors on hospital inpatient costs, with different models estimated for different follow-up periods. A similar regression analysis was performed separately for OR costs and all other hospital costs. Results Patients were predominantly women (n=415 or 86%) with an average age of 48 (18–82) years and an average follow-up of 4.8 (2–8) years. Total hospital costs averaged $120,394, with primary surgery averaging $103,143 and total readmission costs averaging $67,262 per patient with a readmission (n=130 or 27% of all patients). Operating room costs averaged $70,514 per patient, constituting the majority (59%) of total hospital costs. Average total hospital costs across all patients significantly increased (p<.01) after primary surgery, from $111,807 at 1-year follow-up to $126,323 at 4-year follow-up. Regression results also revealed physician preference as the largest determinant of OR costs, accounting for $14,780 of otherwise unexplained OR cost differences across patients, with no significant physician effects on all other non-OR costs (p<.05). Conclusions The incidence of readmissions increased the average cost of ASD surgery by more than 70%, illustrating the financial burden of revisions/reoperations; however, the cost burden resulting from readmissions appeared to taper off within 5 years after surgery. The estimated impact of physician preference on OR costs also highlights the variation in current practice and the opportunity for large cost reductions via a more standardized approach in the use of implants and biologics.
Social cognition matures dramatically during adolescence and into early adulthood, supported by continued improvements in inhibitory control. During this time, developmental changes in interpreting ...and responding to social signals such as facial expressions also occur. In the present study, subjects performed a Go No‐Go task that required them to respond or inhibit responding based on threat or safety cues present in facial expressions. Subjects (N = 112) were divided into three age groups: adolescent (12–15 years), emerging adult (18–25 years) and adult (26–44 years). Analyses revealed a significant improvement in accuracy on No‐Go trials, but not Go trials, during both safe and threat face conditions, with changes evident through early adulthood. In order to better identify the decision‐making processes responsible for these changes in inhibitory control, a drift diffusion model (DDM) was fit to the accuracy and reaction time data, generating measures of caution, response bias, nondecision time (encoding + motor response), and drift rate (face processing efficiency). Caution and nondecision time both increased significantly with age while bias towards the Go response decreased. Drift rate analyses revealed significant age‐related improvements in the ability to map threat faces to a No‐Go response while drift rates on all other trial types were equivalent across age groups. These results suggest that both stimulus‐independent and stimulus‐dependent processes contribute to improvements in inhibitory control in adolescence with processing of negative social cues being specifically impaired by self‐regulatory demands. Findings from this novel investigation of emotional responsiveness integrated with inhibitory control may provide useful insights about healthy development that can be applied to better understand adolescent risk‐taking behavior and the elevated incidence of related forms of psychopathology during this period of life.
Social cognition matures dramatically during adolescence and into early adulthood, supported by continued improvements in inhibitory control. During this time, developmental changes in interpreting and responding to social signals such as facial expressions also occur. In the present study, subjects performed a Go No‐Go task that required them to respond or inhibit responding based on threat or safety cues present in facial expressions.
ABSTRACT
Image slicing is a powerful technique in astronomy. It allows the instrument designer to reduce the slit width of the spectrograph, increasing spectral resolving power whilst retaining ...throughput. Conventionally this is done using bulk optics, such as mirrors and prisms, however, more recently astrophotonic components known as photonic lanterns and photonic reformatters have also been used. These devices reformat the multimode input light from a telescope into single-mode outputs, which can then be re-arranged to suit the spectrograph. The photonic dicer (PD) is one such device, designed to reduce the dependence of spectrograph size on telescope aperture and eliminate modal noise. We simulate the PD, by optimizing the throughput and geometrical design using soapy and BeamProp. The simulated device shows a transmission between 8 and 20 per cent, depending upon the type of adaptive optics correction applied, matching the experimental results well. We also investigate our idealized model of the PD and show that the barycentre of the slit varies only slightly with time, meaning that the modal noise contribution is very low when compared to conventional fibre systems. We further optimize our model device for both higher throughput and reduced modal noise. This device improves throughput by 6.4 per cent and reduces the movement of the slit output by 50 per cent, further improving stability. This shows the importance of properly simulating such devices, including atmospheric effects. Our work complements recent work in the field and is essential for optimizing future photonic reformatters.
During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the ...more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the “immune privileged/specialized” milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of “SCI disease” and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because inflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, “compartimentalized” investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS are influenced by systemic immune challenges and that the immune system is ‘hardwired’ into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and “neurogenic” spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired “host-defense” and trauma-induced autoimmunity.
The physics of mesoscopic electronic systems has been explored for more
than 15 years. Mesoscopic phenomena in transport processes occur when the
wavelength or the coherence length of the carriers ...becomes comparable to,
or larger than, the sample dimensions. One striking result in this domain
is the quantization of electrical conduction, observed in a quasi-one-dimensional
constriction formed between reservoirs of two-dimensional electron gas. The conductance of this system is determined by the number of
participating quantum states or 'channels' within the constriction;
in the ideal case, each spin-degenerate channel contributes a quantized unit
of 2e2/h to the electrical conductance. It has
been speculated that similar behaviour should be observable for thermal transport in mesoscopic phonon systems. But experiments attempted in this
regime have so far yielded inconclusive results.
Here we report the observation of a quantized limiting value for the thermal
conductance, Gth, in suspended insulating nanostructures
at very low temperatures. The behaviour we observe is consistent with predictions for phonon transport in a ballistic, one-dimensional channel:
at low temperatures, Gth approaches a maximum value
of g0 = π2k
2BT/3h, the universal
quantum of thermal conductance.
Autonomic dysregulation is frequent in acute ischemic stroke. Several studies concluded that imbalance between sympathetic and parasympathetic cardiovascular function predisposes to malignant cardiac ...arrhythmia. However, there are few data on cardiovascular autonomic function in post-acute stroke patients.
To study cardiovascular autonomic function 18 to 43 months after lacunar stroke.
We continuously monitored R-R intervals (RR(int)), mean blood pressure (BP(mean)), and respiration in 15 patients (8 women, aged 43 to 73 years) after right-sided stroke, in 13 patients (7 women, aged 50 to 75 years) after left-sided stroke, and in 21 age- and sex-matched controls at rest. We used autoregressive spectral analysis to assess sympathetic and parasympathetic modulation as powers of RR(int) and BP(mean) oscillations in the low-frequency (LF: 0.04 to 0.15 Hz) and high-frequency bands (HF: 0.15 to 0.5 Hz).
Mean values of RR(int), BP(mean), and respiratory frequency did not differ between patients after right- or left-sided stroke and controls (p > 0.05). Patients after right-sided stroke showed a trend toward elevated LF power of RR(int) as compared with patients after left-sided stroke and controls (p < 0.10). HF powers of RR(int) were reduced in patients after right- and left-sided stroke as compared with controls (p < 0.05). LF/HF ratio of RR(int) was elevated in patients after right-sided stroke as compared with patients after left-sided stroke and controls (p < 0.05).
Irrespective of the side of the ischemia, post-acute stroke patients showed a parasympathetic cardiac deficit. Additionally, sympathetic cardiovascular modulation was increased in patients after right-sided stroke. Post-acute stroke patients might be at an increased risk for cardiac arrhythmia after unopposed sympathetic stimulation.
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