Two photons everywhere.

We discuss two-photon physics, taking for illustration the particular but topical case of resonance fluorescence. We show that the basic concepts of interferences and correlations provide at the two-photon level an independent and drastically different picture than at the one-photon level, with landscapes of correlations that reveal various processes by spanning over all the possible frequencies at which the system can emit. Such landscapes typically present lines of photon bunching and circles of antibunching. The theoretical edifice to account for these features rests on two pillars: (i) a theory of frequency-resolved photon correlations and (ii) admixing classical and quantum fields. While experimental efforts have been to date concentrated on correlations between spectral peaks, strong correlations exist between photons emitted away from the peaks, which are accessible only through multi-photon observables. These could be exploited for both fundamental understanding of quantum-optical processes as well as applications by harnessing these unsuspected resources. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'.

Quasichiral Interactions between Quantum Emitters at the Nanoscale.

We present a combined classical and quantum electrodynamics description of the coupling between two circularly polarized quantum emitters held above a metal surface supporting surface plasmons. Depending on their position and their natural frequency, the emitter-emitter interactions evolve from being reciprocal to nonreciprocal, which makes the system a highly tunable platform for chiral coupling at the nanoscale. By relaxing the stringent material and geometrical constraints for chirality, we explore the interplay between coherent and dissipative coupling mechanisms in the system. Thus, we reveal a quasichiral regime in which its quantum optical properties are governed by its subradiant state, giving rise to extremely sharp spectral features and strong photon correlations.

Clinical nutrition counselling service in the veterinary hospital: retrospective analysis of equine patients and nutritional considerations.

Nutrition plays a very important role in the healthy and in the ill horse. Although research in this field clearly shows that incorrect nutritional practices may lead to severe pathologies, inappropriate feeding plans often continue to be used. A clinical nutrition counselling (CNC) service could thus be of great use to both horse owners and veterinarians. The aim of this study was to provide information on equine patients referred to the CNC service of the University of Turin and to provide standard dietary protocols as used in our Veterinary Teaching Hospital for the most common nutrition-related pathologies. The data were obtained by retrospective analysis of the nutritional records of referred equine patients. The data collected included information about anamnesis, nutritional assessment, current diet, referring person and follow-up of each patient. Sixty-one horses were included in the study. The majority were adult males. The most common breeds were the Italian Saddle Horse and the Friesian Horse. Old horses (>19 years) had a statistically lower BCS than brood mares or other adult horses (p < 0.01). The most common nutritional pathologies were chronic weight loss (CWL), chronic diarrhoea (CD) and equine gastric ulcer syndrome. All horses received first-cut meadow hay; 85% also ate concentrates. Young horses (<2 years) received more hay as a percentage of body weight (BW) than old horses or adults. The hay percentage of BW per day given to animals with CWL was statistically higher than those with CD (p < 0.01). The concentrate percentage of BW given to old horses was statistically lower compared to that given to young horses (p < 0.05). The concentrate percentage of BW per day given to horses with colic was statistically higher than that given to horses with CD (p < 0.05). 28% of cases were referred by the owner and 72% by a veterinarian. Follow-up evaluation was deemed to be 'good' in 92% cases and 'poor' in 8%. In summary, the CNC service could provide an epidemiological observatory to study the prevalence of nutritional issues in the equine population.

Erratum: Theory of Frequency-Filtered and Time-Resolved N-Photon Correlations [Phys. Rev. Lett. 109, 183601 (2012)].

This corrects the article DOI: 10.1103/PhysRevLett.109.183601.

Exciting Polaritons with Quantum Light.

We discuss the excitation of polaritons-strongly coupled states of light and matter-by quantum light, instead of the usual laser or thermal excitation. As one illustration of the new horizons thus opened, we introduce "Mollow spectroscopy"-a theoretical concept for a spectroscopic technique that consists of scanning the output of resonance fluorescence onto an optical target-from which weak nonlinearities can be read with high precision even in strongly dissipative environments.

Collective fluid dynamics of a polariton condensate in a semiconductor microcavity.

Semiconductor microcavities offer unique systems in which to investigate the physics of weakly interacting bosons. Their elementary excitations, polaritons-mixtures of excitons and photons-can accumulate in macroscopically degenerate states to form various types of condensate in a wide range of experimental configurations, under either incoherent or coherent excitation. Condensates of polaritons have been put forward as candidates for superfluidity, and the formation of vortices as well as elementary excitations with linear dispersion are actively sought as evidence to support this. Here, using a coherent excitation triggered by a short optical pulse, we have created and set in motion a macroscopically degenerate state of polaritons that can be made to collide with a variety of defects present in the microcavity. Our experiments show striking manifestations of a coherent light-matter packet, travelling at high speed (of the order of one per cent of the speed of light) and displaying collective dynamics consistent with superfluidity, although one of a highly unusual character as it involves an out-of-equilibrium dissipative system. Our main results are the observation of a linear polariton dispersion accompanied by diffusionless motion; flow without resistance when crossing an obstacle; suppression of Rayleigh scattering; and splitting into two fluids when the size of the obstacle is comparable to the size of the wave packet. This work opens the way to the investigation of new phenomenology of out-of-equilibrium condensates.

Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis.

BACKGROUND AND PURPOSE: It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes. PATIENTS AND METHODS: From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation. RESULTS: Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15). CONCLUSION: Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients.

Ultrafast Control and Rabi Oscillations of Polaritons.

We report the experimental observation and control of space and time-resolved light-matter Rabi oscillations in a microcavity. Our setup precision and the system coherence are so high that coherent control can be implemented with amplification or switching off of the oscillations and even erasing of the polariton density by optical pulses. The data are reproduced by a quantum optical model with excellent accuracy, providing new insights on the key components that rule the polariton dynamics.

Functional foods and cardiometabolic diseases* International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

Comparative MRI analysis of the forebrain of three sauropsida models.

The study of the brain by magnetic resonance imaging (MRI) allows to obtain detailed anatomical images, useful to describe specific encephalic structures and to analyze possible variabilities. It is widely used in clinical practice and is becoming increasingly used in veterinary medicine, even in exotic animals; however, despite its potential, its use in comparative neuroanatomy studies is still incipient. It is a technology that in recent years has significantly improved anatomical resolution, together with the fact that it is non-invasive and allows for systematic comparative analysis. All this makes it particularly interesting and useful in evolutionary neuroscience studies, since it allows for the analysis and comparison of brains of rare or otherwise inaccessible species. In the present study, we have analyzed the prosencephalon of three representative sauropsid species, the turtle Trachemys scripta (order Testudine), the lizard Pogona vitticeps (order Squamata) and the snake Python regius (order Squamata) by MRI. In addition, we used MRI sections to analyze the total brain volume and ventricular system of these species, employing volumetric and chemometric analyses together. The raw MRI data of the sauropsida models analyzed in the present study are available for viewing and downloading and have allowed us to produce an atlas of the forebrain of each of the species analyzed, with the main brain regions. In addition, our volumetric data showed that the three groups presented clear differences in terms of total and ventricular brain volumes, particularly the turtles, which in all cases presented distinctive characteristics compared to the lizards and snakes.

Effect of adjuvant trastuzumab treatment in conventional clinical setting: an observational retrospective multicenter Italian study.

Clinical trials have shown the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancers, but routine clinical use awaits evaluation of compliance, safety, and effectiveness. Adjuvant trastuzumab-based therapy in routine clinical use was evaluated in the retrospective study GHEA, recording 1,002 patients treated according to the HERA protocol between March 2005 and December 2009 in 42 Italian oncology departments; 874 (87.23 %) patients completed 1-year trastuzumab treatment. In 128 patients (12.77 %), trastuzumab was withdrawn due to cardiac or non-cardiac toxicity (28 and 29 patients, respectively), disease progression (5 patients) or the clinician's decision (66 patients). In addition, 156 patients experienced minor non-cardiac toxicities; 10 and 44 patients showed CHF and decreased LVEF, respectively, at the end of treatment. Compliance and safety of adjuvant trastuzumab-based therapy in Italian hospitals were high and close to those reported in the HERA trial. With a median follow-up of 32 months, 107 breast cancer relapses were recorded (overall frequency, 10.67 %), and lymph node involvement, estrogen receptor negativity, lymphoid infiltration, and vascular invasion were identified as independent prognostic factors for tumor recurrence, indicating that relapses were associated with advanced tumor stage. Analysis of site and frequency of distant metastases showed that bone metastases were significantly more frequent during or immediately after trastuzumab (<18 months from the start of treatment) compared to recurrences in bone after the end of treatment and wash-out of the drug (>18 months from the start of treatment) (35.89 vs. 14.28 %, p = 0.0240); no significant differences were observed in recurrences in the other recorded body sites, raising the possibility that the protection exerted by trastuzumab is lower in bone metastases.

Very high prevalence of ultrasound thyroid scan abnormalities in healthy volunteers in Modena, Italy.

BACKGROUND: Italy is characterized by high prevalence of goiter. To date, only limited data about the prevalence of goiter in the Italian adult population are available. AIM: To investigate the prevalence of thyroid ultrasound abnormalities in adults unaware of any thyroid disease and evaluate the rate of differentiated thyroid cancer (DTC) obtained by this intervention. METHODS: Ultrasound (US) thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy. One hundred and thirty-five women and 66 men (no.= 201), unaware of any thyroid disease (mean age of 46 ± 10.7 yr) underwent their first thyroid US scan. RESULTS: US thyroid abnormalities were found in 101 subjects (50.3%): 91 nodular goiters (45.2%) and 13 US-thyroiditis (6.5%) associated with positive auto-antibodies in 11 of them. Seventeen subjects (18%) with nodules underwent US-fine needle aspiration biopsy with the following cytological class (C) outcome: 14 patients C2 (82%), 1 patient C3 (6%), 2 patients had C4 (12%), the latter received histological confirmation. CONCLUSIONS: The prevalence of thyroid abnormalities is very high in subjects unaware of any thyroid disease. DTC was found in 1% of subjects and in 2% of those affected by nodular goiter. Compared to the detection rate of the well-established screening programs for breast (0.45%) and colorectal (0.27%) cancer, the prevalence of DTC seems to be much higher. Thyroid US screening could allow the detection of DTC in asymptomatic subjects and this diagnosis often includes DTC at an advanced stage. Thus, US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases.

Evaluation of bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) in hemodialysis patients.

UNLABELLED: Hemodialyzed patients have decreased bone strength not completely characterized. We evaluated bone microarchitecture in hemodialysis patients and compared it to that of subjects without renal disease by high-resolution peripheral quantitative computed tomography (HR-pQCT). Hemodialysis patients have a marked decreased in cortical density, thickness, and area with significant reduction in trabecular parameters that correlated with the severity of secondary hyperparathyroidism only in women. INTRODUCTION: Although fracture risk is greatly increased in dialysis patients, the corresponding decreased in bone strength has not been completely characterized. METHODS: We evaluated volumetric bone mineral density (vBMD) and bone microstructure by HR-pQCT at the distal radius and tibia in 50 hemodialyzed (HD) patients (30 females, mean age 53.2 ± 6 years and 20 males, mean age 59.1 ± 11 years) and 50 sex- and age-matched controls. RESULTS: At the distal radius HD, women showed a 29% reduction in total and trabecular density and trabecular bone volume fraction (p < 0.0001) compared to controls. Trabecular number was reduced by 25% (p < 0.0001), while trabecular separation was increased by 51%. Cortical thickness (-40%, p < 0.0001) and cortical area (-42%, p < 0.0001) were the parameters most reduced, while compact density was the parameter least reduced (-15%, p < 0.0001). Similar findings were found at the tibia. In HD men, HR-pQCT at the distal radius and tibia showed a reduction in volumetric density and microstructure parameters to a lesser extent than in women. In the hemodialyzed group, cortical thickness at the radius was negatively correlated with age both in women and men. At the distal radius and tibia, we found significant negative correlations between Log iPTH and total alkaline phosphatase with cortical vBMD(r = -0.48, p < 0.01; r = -0.69, p < 0.001), thickness (-0.37, p < 0.05; r = -0.60, p < 0.001), and area ((r = -0.43, p = 0.02; r = -0.65, p < 0.001) but only in women. CONCLUSION: We conclude that hemodialysis patients have a marked decreased in cortical density, thickness, and area with significant reduction in trabecular parameters that correlated with the severity of secondary hyperparathyroidism only in women.

Theory of frequency-filtered and time-resolved N-photon correlations.

A theory of correlations between N photons of given frequencies and detected at given time delays is presented. These correlation functions are usually too cumbersome to be computed explicitly. We show that they are obtained exactly through intensity correlations between two-level sensors in the limit of their vanishing coupling to the system. This allows the computation of correlation functions hitherto unreachable. The uncertainties in time and frequency of the detection, which are necessary variables to describe the system, are intrinsic to the theory. We illustrate the power of our formalism with the example of the Jaynes-Cummings model, by showing how higher order photon correlations can bring new insights into the dynamics of open quantum systems.

Longitudinal studies of ischemic penumbra by using 18F-FDG PET and MRI techniques in permanent and transient focal cerebral ischemia in rats.

At present, the goal of stroke research is the identification of a potential recoverable tissue surrounding the ischemic core, suggested as ischemic penumbra, with the aim of applying a treatment that attenuates the growth of this area. Our purpose was to determine whether a combination of imaging techniques, including (18)F-FDG PET and MRI could identify the penumbra area. Longitudinal studies of (18)F-FDG PET and MRI were performed in rats 3 h, 24 h and 48 h after the onset of ischemia. A transient and a permanent model of focal cerebral ischemia were performed. Regions of interest were located, covering the ischemic core, the border that progresses to infarction (recruited tissue), and the border that recovers (recoverable tissue) with early reperfusion. Analyses show that permanent ischemia produces severe damage, whereas the transient ischemia model does not produce clear damage in ADC maps at the earliest time studied. The only significant differences between values for recoverable tissue, (18)F-FDG (84±2%), ADC (108±5%) and PWI (70±8%), and recruited tissue, (18)F-FDG (77±3%), ADC (109±4%) and PWI (77±4%), are shown in (18)F-FDG ratios. We also show that recoverable tissue values are different from those in non-infarcted tissue. The combination of (18)F-FDG PET, ADC and PWI MRI is useful for identification of ischemic penumbra, with (18)F-FDG PET being the most sensitive approach to its study at early times after stroke, when a clear DWI deficit is not observed.

DNA methylation in repetitive elements and Alzheimer disease.

Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT-α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT-α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6%5mC, volunteers: 83.1%5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9%5mC; MMSE≤22: 83.2%5mC; p=0.05). Our data suggest that LINE-1 methylation may lead to a better understanding of AD pathogenesis and course, and may contribute to identify novel markers useful to assess risk stratification. Further prospective investigations are warranted to evaluate the dynamics of DNA methylation from early-stage AD to advanced phases of the disease.

CT-guided cryoablation of both breast cancer and lymph node axillary metastasis.

Breast conservation is a major goal of cancer treatment. Many different minimally invasive options have been considered such as cryoablation. This technique is the best visualized of all ablation techniques due to the phase change during ice formation. We describe a case of breast cancer with lymph node axillary metastasis treated by CT-guided cryoablation. Cryoablation may have unique benefits for cost-effective outpatient breast cancer therapy using only local anesthesia and/or mild sedation.

Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases.

BACKGROUND: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). PATIENTS AND METHODS: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. RESULTS: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. CONCLUSIONS: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Effect of pure dephasing on the Jaynes-Cummings nonlinearities.

We study the effect of pure dephasing on a two-level system in strong coupling in the nonlinear regime with the single mode of a cavity. The photoluminescence spectrum of the cavity has a robust tendency to display triplet structures, instead of the expected Jaynes-Cummings pairs of doublets at the incommensurate frequencies +/- (square root n +/- square root (n-1)) for integer n. We discuss recent experimental works that may already manifest signatures of single photon nonlinearities.