Fc-independent functions of anti-CTLA-4 antibodies contribute to anti-tumor efficacy.

Ipilimumab, a monoclonal antibody that recognizes cytotoxic T-lymphocyte associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by the FDA to treat metastatic melanoma patients. Multiple preclinical studies have proposed that Fc effector functions of anti-CTLA-4 therapy are required for anti-tumor efficacy, in part, through the depletion of intratumoral regulatory T cells (Tregs). However, the contribution of the Fc-independent functions of anti-CTLA-4 antibodies to the observed efficacy is not fully understood. H11, a non-Fc-containing single-domain antibody (VHH) against CTLA-4, has previously been demonstrated to block CTLA-4-ligand interaction. However, in vivo studies demonstrated lack of anti-tumor efficacy with H11 treatment. Here, we show that a half-life extended H11 (H11-HLE), despite the lack of Fc effector functions, induced potent anti-tumor efficacy in mouse syngeneic tumor models. In addition, a non-Fc receptor binding version of ipilimumab (Ipi-LALAPG) also demonstrated anti-tumor activity in the absence of Treg depletion. Thus, we demonstrate that Fc-independent functions of anti-CTLA-4 antibodies contributed to anti-tumor efficacy, which may indicate that non-Treg depleting activity of anti-CTLA-4 therapy could benefit cancer patients in the clinic.

When Chiral Photons Meet Chiral Fermions: Photoinduced Anomalous Hall Effects in Weyl Semimetals.

The Weyl semimetal is characterized by three-dimensional linear band touching points called Weyl nodes. These nodes come in pairs with opposite chiralities. We show that the coupling of circularly polarized photons with these chiral electrons generates a Hall conductivity without any applied magnetic field in the plane orthogonal to the light propagation. This phenomenon comes about because with all three Pauli matrices exhausted to form the three-dimensional linear dispersion, the Weyl nodes cannot be gapped. Rather, the net influence of chiral photons is to shift the positions of the Weyl nodes. Interestingly, the momentum shift is tightly correlated with the chirality of the node to produce a net anomalous Hall signal. Application of our proposal to the recently discovered TaAs family of Weyl semimetals leads to an order-of-magnitude estimate of the photoinduced Hall conductivity which is within the experimentally accessible range.

Robust distant entanglement generation using coherent multiphoton scattering.

We describe a protocol to entangle two qubits at a distance by using resonance fluorescence. The scheme makes use of the postselection of large and distinguishable fluorescence signals corresponding to entangled and unentangled qubit states and has the merits of both high success probability and high entanglement fidelity owing to the multiphoton nature. Our result shows that the entanglement generation is robust against photon fluctuations in the fluorescence signals for a wide range of driving fields. We also demonstrate that this new protocol has an average entanglement duration within the decoherence time of corresponding qubit systems, based on current experimental photon efficiency.

Detection of Herba Aristolochia Mollissemae in a patient with unexplained nephropathy.

The authors report a case of unexplained nephropathy 2 months after ingestion of Herba Aristolochia Mollissemae in a patient with long-standing Crohn's disease and recently diagnosed carcinoma of the colon. It presented as a relentlessly progressing hypocellular interstitial nephritis 5 months after cessation of an earlier course of mesalazine. The patient finally had end-stage renal failure 12 months after taking herbs and required hemodialysis. Aristolochic acid (AA) was detected in the herbal sample of Herba Aristolochia Mollissemae by high-performance liquid chromatography-diode array detection and electrospray ionization-tandem mass spectrometry. Specific AA-DNA adducts were detected in the renal biopsy by 32 P-postlabelling analysis. Transitional cell carcinoma was diagnosed 5 months after herb ingestion. It was found that the originally prescribed nonnephrotoxic herb had been substituted by AA-containing Herba Aristolochia Mollissemae at the wholesaler level. Although AA-associated nephropathy could not be proved conclusively, the current case contributed to the withdrawal of the AA-related herbs by the local health authority in Hong Kong. Physicians should be on the alert for herbal nephrotoxicity by possible replacement of nontoxic herbs by nephrotoxic herbs.

Adequacy targets in peritoneal dialysis.

Adequate solute and fluid removal are the cornerstones of dialysis treatment. In peritoneal dialysis, what constitutes adequate removal, has been hitherto controversial, based as it was on DOQI guidelines. There are now 2 randomised controlled trials that address solute removal--both indicate that the minimal Kt/V needs to be 1.7. This needs to be adjusted in individual cases based on clinical and other parameters. Fluid removal and blood pressure control are also important adequacy parameters. Sub-clinical fluid overload is a common feature and relates to left ventricular hypertrophy. This also needs addressing but estimating fluid status is difficult.

Entanglement tongue and quantum synchronization of disordered oscillators.

We study the synchronization of dissipatively coupled van der Pol oscillators in the quantum limit, when each oscillator is near its quantum ground state. Two quantum oscillators with different frequencies exhibit an entanglement tongue, which is the quantum analog of an Arnold tongue. It means that the oscillators are entangled in steady state when the coupling strength is greater than a critical value, and the critical coupling increases with detuning. An ensemble of many oscillators with random frequencies still exhibits a synchronization phase transition in the quantum limit, and we analytically calculate how the critical coupling depends on the frequency disorder. Our results can be experimentally observed with trapped ions or neutral atoms.

Risk factors for poor outcome of fungal peritonitis in Chinese patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: Fungal peritonitis is rare among end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), but when it occurs, it is associated with a high risk of mortality and peritoneal membrane failure. In the present study, we identified risk factors for poor outcome and examined the effect of treatment profile on outcome in fungal peritonitis. PATIENTS AND METHODS: We identified cases of fungal peritonitis in CAPD patients in a regional dialysis center and analyzed the possible risk factors for poor outcome in fungal peritonitis. To estimate the amount of dextrose presented to the peritoneum, we scored the dextrose content of the peritoneal dialysis fluid used by the patient at the time of admission to hospital (1 point to each bag of 1.5% fluid, 2 points to each bag of 2.3% or 2.5% fluid, and 3 points to each bag of 4.25% fluid daily). RESULTS: Among 471 episodes of CAPD-related peritonitis in 7.8 years, we identified 22 episodes of fungal peritonitis (4.7%). The ratio of men to women in the fungal peritonitis group was 1.4:1. Seventeen patients (77.3%) practiced dialysis without a helper. Within the 3 months preceding the fungal peritonitis, 12 patients (55%) had had bacterial peritonitis. Among the cases of fungal peritonitis, we identified 9 cases of Candida parapsilosis and 13 cases of non C. parapsilosis. All of the patients received fluconazole, and 7 patients (31.8%) also received flucytosine. The Tenckhoff catheter was removed in 17 patients (77.3%). Eight patients (36.4%) either died or lost peritoneal function. The risk of mortality was increased if the fungal organism was C. parapsilosis [odds ratio (OR): 4.25; 95% confidence interval (CI): 1.8 to 10.0; p = 0.002], if a helper was involved (OR: 11.3; 95% CI: 1.1 to 114; p = 0.024), or if CAPD duration was more than 26 months (OR: 2.2; 95% CI: 1.3 to 3.5; p = 0.034). Addition of flucytosine to fluconazole did not significantly improve the mortality rate in either the C. parapsilosis or non C. parapsilosis group. Multivariate analysis showed that C. parapsilosis was an independent factor associated with mortality (p = 0.013). A dextrose score greater than 5 was associated with a trend toward increased risk of peritoneal failure (OR: 3.4; 95% CI: 1.6 to 7.1; p = 0.021). CONCLUSION: C. parapsilosis is an independent risk factor for mortality in fungal peritonitis.

Nutritional requirements and actual dietary intake of continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: Nutritional status is related to morbidity and mortality in the continuous ambulatory peritoneal dialysis (CAPD) population. In the present study, we compared the dietary intake of CAPD patients with their requirements for calorie and protein nutrition and with the recommended intakes of potassium and phosphate. DESIGN: Patients were recruited from the CAPD clinic. Desirable body weight was derived from the height of the individual patients and the desirable body mass index (BMI) for adult Asians. The calorie requirement was calculated by multiplying desirable body weight by 30 kcal. The protein requirement was calculated by multiplying desirable body weight by 1.2 - 1.5, according to serum albumin level. The K requirement was set at 3500 mg daily, and the PO(4) requirement, at 1000 mg daily. The actual dietary intake of individual patients was estimated from dietary history by a computer software program. RESULTS: The study included 57 patients who had been on CAPD for 22.1 +/- 23.5 months. Of the 57 patients, 8 patients (14.0%) were below the desirable BMI range, 20 (35.1%) were within the range, and 29 (50.9%) were above the range. By subjective global assessment (SGA), 45 patients (78.9%) were mildly-to-moderately malnourished, and 12 (21.1%) well nourished. Serum albumin was 32.1 +/- 4.7 g/L. Patients met 98% +/- 35.7% (range: 33% - 224%) of their nutritional requirement for calories and 92.1% +/- 37.7% (range: 22% - 202%) of their nutritional requirement for protein. Only 23 patients (40.4%) reached the target for calorie intake, and only 22 (38.6%) reached the target for protein intake. Excess K intake was seen in 1 patient (1.8%), and excess PO(4) intake, in 6 patients (10.5%). Actual dietary intake was not related to BMI or SGA score. CONCLUSION: Most CAPD patients had inadequate calorie and protein intakes. Calorie and protein intakes were not related to BMI and SGA scores. Compliance with recommended K and PO(4) intakes was good.

Nutritional assessment of continuous ambulatory peritoneal dialysis patients by bioelectrical impedance.

OBJECTIVE: The Dialysis Outcomes Quality Initiative (DOQI) guidelines suggest that anthropometric measurements are useful in assessment of nutrition. However, the technique is operator-dependent and time consuming. To estimate fat-free mass and fat mass, bioelectrical impedance analysis (BIA) measures the impedance of an electrical current passing through the body. Our aim in the present study was to validate the use of BIA in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: We recruited patients from the CAPD clinic. The biceps, triceps, subscapular, and suprailiac skinfold thickness were measured by Harpenden skinfold calipers (British Indicators, Burgess Hill, West Sussex, U.K.). Using a linear regression equation (Durin and Womersley) and the Siri equation, we calculated percentage body fat composition from the anthropometric measurements. For BIA assessment, fat composition was measured using the Body Composition Analyzer (TBF-300GS: Tanita Corporation of America, Arlington Heights, IL, U.S.A.). RESULTS: We recruited a total of 60 patients who had been on CAPD for 21.8 +/- 23 months. The percentage of body fat in the study group as estimated by anthropometry was 27.5% +/- 8.6% (range: 5.78% - 40.4%). By BIA, the percentage of body fat was 17.6% +/- 8.9% (range: 2.4% - 42.3%). The results by the two methods were highly correlated (r = 0.712, p < 0.001). By paired t-test, the mean difference in body fat composition using the two different methods was 9.9% +/- 6.6% (p < 0.001). CONCLUSIONS: Measurement of body fat composition in CAPD patients by BIA and by anthropometry were highly correlated. The body fat composition measured by BIA was lower than that measured by anthropometry. The BIA method is simple and noninvasive. It may play a role in monitoring trend of body composition in CAPD patients in an outpatient setting.