Emerging treatment options for the management of brain metastases in patients with HER2-positive metastatic breast cancer.

The widespread use of trastuzumab in the past decade has led to a significant and measureable improvement in the survival of patients with human epidermal growth factor receptor-2 (HER2) overexpressing breast cancer, and in many ways has redefined the natural history of this aggressive breast cancer subtype. Historically, survival in patients with HER2-positive disease was dictated by the systemic disease course, and what appears to be the central nervous system (CNS) tropism associated with HER2-amplified tumors was not clinically evident. With improved systemic control and prolonged survival, the incidence of brain metastases has increased, and CNS disease, often in the setting of well-controlled extracranial disease, is proving to be an increasingly important and clinically challenging cause of morbidity and mortality in patients with HER2-positive advanced breast cancer. This review summarizes the known clinical data for the systemic treatment of HER2-positive CNS metastases and includes information about ongoing clinical trials of novel therapies as well as emerging strategies for early detection and prevention

Scalp cooling with adjuvant/neoadjuvant chemotherapy for breast cancer and the risk of scalp metastases: systematic review and meta-analysis.

PurposeThe risk of scalp metastases in patients using scalp cooling for preservation of hair during chemotherapy has been a concern but is poorly described.MethodsA systematic review and meta-analysis of longitudinal studies was undertaken to evaluate the effect of scalp cooling versus no scalp cooling on the risk of scalp metastasis in patients treated for breast cancer with chemotherapy. Electronic databases, journal specific, and hand searches of articles identified were searched. Patients were matched based on disease, treatment, lack of metastatic disease, and sex.ResultsA total of 24 full-text articles were identified for review. Of these articles, ten quantified the incidence of scalp metastasis with scalp cooling over time. For scalp cooling, 1959 patients were evaluated over an estimated mean time frame of 43.1 months. For no scalp cooling, 1238 patients were evaluated over an estimated mean time frame of 87.4 months. The incidence rate of scalp metastasis in the scalp cooling group versus the no scalp cooling group was 0.61% (95% CI 0.32-1.1%) versus 0.41% (95% CI 0.13-0.94%); P = 0.43.ConclusionThe incidence of scalp metastases was low regardless of scalp cooling. This analysis suggests that scalp cooling does not increase the incidence of scalp metastases

Stabilising entanglement by quantum jump-based feedback

We show that direct feedback based on quantum jump detection can be used to generate entangled steady states. We present a strategy that is insensitive to detection inefficiencies and robust against errors in the control Hamiltonian. This feedback procedure is also shown to overcome spontaneous emission effects by stabilising states with high degree of entanglement.Comment: 5 pages, 4 figure

Continuous measurement feedback control of a Bose-Einstein condensate using phase contrast imaging

We consider the theory of feedback control of a Bose-Einstein condensate (BEC) confined in a harmonic trap under a continuous measurement constructed via non-destructive imaging. A filtering theory approach is used to derive a stochastic master equation (SME) for the system from a general Hamiltonian based upon system-bath coupling. Numerical solutions for this SME in the limit of a single atom show that the final steady state energy is dependent upon the measurement strength, the ratio of photon kinetic energy to atomic kinetic energy, and the feedback strength. Simulations indicate that for a weak measurement strength, feedback can be used to overcome heating introduced by the scattering of light, thereby allowing the atom to be driven towards the ground state.Comment: 4 figures, 11 page

Generating controllable atom-light entanglement with a Raman atom laser system

We introduce a scheme for creating continuous variable entanglement between an atomic beam and an optical field, by using squeezed light to outcouple atoms from a BEC via a Raman transition. We model the full multimode dynamics of the atom laser beam and the squeezed optical field, and show that with appropriate two-photon detuning and two-photon Rabi frequency, the transmitted light is entangled in amplitude and phase with the outcoupled atom laser beam. The degree of entanglement is controllable via changes in the two-photon Rabi frequency of the outcoupling process.Comment: 4 pages, 4 figure

Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. Millennium Cohort Study

Background: Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. Objectives: To identify early-life risk factors for eczema, and to explore how early-life risk factors explain any differences in eczema. Methods: We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early-life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. Results: Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree-level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31–1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1–6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early-life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03–1·50) in the group with the highest educational qualifications compared with the least. Conclusions: In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early-life factors including not smoking during pregnancy, breastfeeding and having fewer siblings

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

PurposeTo determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics.Materials and methodsThis retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame.ResultsWe identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019).ConclusionPalonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs

Stability of continuously pumped atom lasers

A multimode model of a continuously pumped atom laser is shown to be unstable below a critical value of the scattering length. Above the critical scattering length, the atom laser reaches a steady state, the stability of which increases with pumping. Below this limit the laser does not reach a steady state. This instability results from the competition between gain and loss for the excited states of the lasing mode. It will determine a fundamental limit for the linewidth of an atom laser beam.Comment: 4 page

A Trade-Off between Somatosensory and Auditory Related Brain Activity during Object Naming But Not Reading.

The parietal operculum, particularly the cytoarchitectonic area OP1 of the secondary somatosensory area (SII), is involved in somatosensory feedback. Using fMRI with 58 human subjects, we investigated task-dependent differences in SII/OP1 activity during three familiar speech production tasks: object naming, reading and repeatedly saying "1-2-3." Bilateral SII/OP1 was significantly suppressed (relative to rest) during object naming, to a lesser extent when repeatedly saying "1-2-3" and not at all during reading. These results cannot be explained by task difficulty but the contrasting difference between naming and reading illustrates how the demands on somatosensory activity change with task, even when motor output (i.e., production of object names) is matched. To investigate what determined SII/OP1 deactivation during object naming, we searched the whole brain for areas where activity increased as that in SII/OP1 decreased. This across subject covariance analysis revealed a region in the right superior temporal sulcus (STS) that lies within the auditory cortex, and is activated by auditory feedback during speech production. The tradeoff between activity in SII/OP1 and STS was not observed during reading, which showed significantly more activation than naming in both SII/OP1 and STS bilaterally. These findings suggest that, although object naming is more error prone than reading, subjects can afford to rely more or less on somatosensory or auditory feedback during naming. In contrast, fast and efficient error-free reading places more consistent demands on both types of feedback, perhaps because of the potential for increased competition between lexical and sublexical codes at the articulatory level