Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis

Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy

Ultra-high-resolution software-defined photonic terahertz spectroscopy

A novel technique for high-resolution 1.5 µm photonics-enabled terahertz (THz) spectroscopy using software control of the illumination spectral line shape (SLS) is presented. The technique enhances the performance of a continuous-wave THz spectrometer to reveal previously inaccessible details of closely spaced spectral peaks. We demonstrate the technique by performing spectroscopy on LiYF4:Ho3+, a material of interest for quantum science and technology, where we discriminate between inhomogeneous Gaussian and homogeneous Lorentzian contributions to absorption lines near 0.2 THz. Ultra-high-resolution (<100 Hz full-width at half maximum) frequency-domain spectroscopy with quality factor Q > 2 × 109 is achieved using an exact frequency spacing comb source in the optical communications band, with a custom uni-traveling-carrier photodiode mixer and coherent down-conversion detection. Software-defined time-domain modulation of one of the comb lines is demonstrated and used to resolve the sample SLS and to obtain a magnetic field-free readout of the electronuclear spectrum for the Ho3+ ions in LiYF4:Ho3+. In particular, homogeneous and inhomogeneous contributions to the spectrum are readily separated. The experiment reveals previously unmeasured information regarding the hyperfine structure of the first excited state in the 5 I8 manifold complementing the results reported in Phys. Rev. B 94, 205132 (2016)

Dietary selenized yeast increases the selenium content whereas organic iron (sqm) has no effect on the iron content of pork

The human health benefits of dietary selenium (Se) and iron (Fe) are well established (Rayman, 1997; Kristensen et al., 2005). Meat and meat products are primary sources of dietary Se and iron for humans. Pork from Se and Fe-supplemented pigs may provide an additional source of these nutrients. However, the effects of supplementation of Se and iron on their status in muscles and effects on pork quality are not clearly defined. This study examined the effects of dietary Se and Fe supplementation on the Se and Fe status and meat quality of pork

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications

Changes in the Th1 : Th2 Cytokine Bias in Pregnancy and the Effects of the Anti-Inflammatory Cyclopentenone Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2

Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2) protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ12,14-Prostaglandin J2 (15dPGJ2) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ2 could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4) synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs) from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ2 or vehicle control and stimulated with phorbol myristyl acetate (PMA)/ionomycin. The percentage of CD4+ cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ2 reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2+ve cells. 15dPGJ2 also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ2 suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL

Differential effects of natural palm oil, chemically- and enzymatically-modified palm oil on weight gain, blood lipid metabolites and fat deposition in a pediatric pig model

<p>Abstract</p> <p>Background</p> <p>Increasing prevalence of obesity and overweight in the Western world, continue to be a major health threat and is responsible for increased health care costs. Dietary intervention studies show a strong positive association between saturated fat intake and the development of obesity and cardiovascular disease. This study investigated the effect of positional distribution of palmitic acid (Sn-1, 2 & 3) of palm oil on cardiovascular health and development of obesity, using weaner pigs as a model for young children.</p> <p>Methods</p> <p>Male and female weaner piglets were randomly allocated to 4 dietary treatment groups: 1) pork lard (LRD); 2) natural palm olein (NPO); 3) chemically inter-esterified PO (CPO) and 4) enzymatically inter-esterified PO (EnPO) as the fat source. Diets were formulated with 11% lard or with palm olein in order to provide 31% of digestible energy from fat in the diet and were balanced for cholesterol, protein and energy across treatments.</p> <p>Results</p> <p>From 8 weeks onwards, pigs on EnPO diet gained (P < 0.05) more weight than all other groups. Feed conversion efficiency (feed to gain) over the 12 week experimental period did not vary between treatment groups. Plasma LDL-C content and LDL-C/HDL-C ratio in pigs fed natural PO tended to be lower compared to all other diets. The natural PO lowered (P < 0.02) the plasma triglyceride (TG) content relative to the lard or EnPO diets, but was not different from the CPO diet. The natural PO diet was associated with lower (P < 0.05) saturated fat levels in subcutaneous adipose tissue than the CPO and EnPO diets that had lower saturated fat levels than the lard diet. Female pigs had lower lean and higher fat and fat:lean ratio in the body compared with male pigs. No difference in weight gain or blood lipid parameters was observed between sexes.</p> <p>Conclusions</p> <p>The observations on plasma TG, muscle and adipose tissue saturated fatty acid contents and back fat (subcutaneous) thickness suggest that natural palm oil may reduce deposition of body fat. In addition, dietary supplementation with natural palm oil containing palmitic acid at different positions in meat producing animals may lead to the production of meat and meat products with lower saturated fats. An increase in fat content and a decrease in lean content in female pigs resulted in an increased body fat:lean ratio but gender had no effect on blood lipid parameters or insulin concentrations.</p

Ultra-stable 25.5 GHz quantum dot mode-locked frequency comb operating up to 120 ℃

We report a frequency comb source based on a quantum dot mode-locked laser that generates a frequency comb with a stable 25.5 GHz mode spacing over an ultra-broad temperature range of 20 °C - 120 °C

Low-noise 1.3 μm InAs/GaAs quantum dot laser monolithically grown on silicon

We report low-noise, high-performance single transverse mode 1.3 μm InAs/GaAs quantum dot lasers monolithically grown on silicon (Si) using molecular beam epitaxy. The fabricated narrow-ridge-waveguide Fabry–Perot (FP) lasers have achieved a room-temperature continuous-wave (CW) threshold current of 12.5 mA and high CW temperature tolerance up to 90°C. An ultra-low relative intensity noise of less than −150  dB/Hz is measured in the 4–16 GHz range. Using this low-noise Si-based laser, we then demonstrate 25.6 Gb/s data transmission over 13.5 km SMF-28. These low-cost FP laser devices are promising candidates to provide cost-effective solutions for use in uncooled Si photonics transmitters in inter/hyper data centers and metropolitan data links

Quantum dot mode-locked frequency comb with ultra-stable 25.5 GHz spacing between 20°C and 120°C

Semiconductor mode-locked lasers (MLLs) are promising frequency comb sources for dense wavelength-division-multiplexing (DWDM) data communications. Practical data communication requires a frequency-stable comb source in a temperature-varying environment and a minimum tone spacing of 25 GHz to support high-speed DWDM transmissions. To the best of our knowledge, however, to date, there have been no demonstrations of comb sources that simultaneously offer a high repetition rate and stable mode spacing over an ultrawide temperature range. Here, we report a frequency comb source based on a quantum dot (QD) MLL that generates a frequency comb with stable mode spacing over an ultrabroad temperature range of 20–120°C. The two-section passively mode-locked InAs QD MLL comb source produces an ultra-stable fundamental repetition rate of 25.5 GHz (corresponding to a 25.5 GHz spacing between adjacent tones in the frequency domain) with a variation of 0.07 GHz in the tone spacing over the tested temperature range. By keeping the saturable absorber reversely biased at − 2    V , stable mode-locking over the whole temperature range can be achieved by tuning the current of the gain section only, providing easy control of the device. At an elevated temperature of 100°C, the device shows a 6 dB comb bandwidth of 4.81 nm and 31 tones with &gt; 36    dB optical signal-to-noise ratio. The corresponding relative intensity noise, averaged between 0.5 GHz and 10 GHz, is − 146    dBc / Hz . Our results show the viability of the InAs QD MLLs as ultra-stable, uncooled frequency comb sources for low-cost, large-bandwidth, and low-energy-consumption optical data communications.Royal Academy of Engineering (RF201617/16/28); Engineering and Physical Sciences Research Council (EP/R041792/1, EP/T01394X/1)