Strong coupling-induced frequency shifts of highly detuned photonic modes in multimode cavities.

Strong coupling between light and molecules is a fascinating topic exploring the implications of the hybridization of photonic and molecular states. For example, many recent experiments have explored the possibility that strong coupling of photonic and vibrational modes might modify chemical reaction rates. In these experiments, reactants are introduced into a planar cavity, and the vibrational mode of a chemical bond strongly couples to one of the many photonic modes supported by the cavity. Some experiments quantify reaction rates by tracking the spectral shift of higher-order cavity modes that are highly detuned from the vibrational mode of the reactant. Here, we show that the spectral position of these cavity modes, even though they are highly detuned, can still be influenced by strong coupling. We highlight the need to consider this strong coupling-induced frequency shift of cavity modes if one is to avoid underestimating cavity-induced reaction rate changes. We anticipate that our work will assist in the re-analysis of several high-profile results and has implications for the design of future strong coupling experiments.

Fusion of deterministically generated photonic graph states.

Entanglement has evolved from an enigmatic concept of quantum physics to a key ingredient of quantum technology. It explains correlations between measurement outcomes that contradict classical physics and has been widely explored with small sets of individual qubits. Multi-partite entangled states build up in gate-based quantum-computing protocols and-from a broader perspective-were proposed as the main resource for measurement-based quantum-information processing1,2. The latter requires the ex-ante generation of a multi-qubit entangled state described by a graph3-6. Small graph states such as Bell or linear cluster states have been produced with photons7-16, but the proposed quantum-computing and quantum-networking applications require fusion of such states into larger and more powerful states in a programmable fashion17-21. Here we achieve this goal by using an optical resonator22 containing two individually addressable atoms23,24. Ring25 and tree26 graph states with up to eight qubits, with the names reflecting the entanglement topology, are efficiently fused from the photonic states emitted by the individual atoms. The fusion process itself uses a cavity-assisted gate between the two atoms. Our technique is, in principle, scalable to even larger numbers of qubits and is the decisive step towards, for instance, a memory-less quantum repeater in a future quantum internet27-29.

Routine 6-Week Outpatient Radiography and Visit in Patients with Conservatively Treated Multiple Rib Fractures: Valuable or a Waste of Resources?

Background: This study investigated the incidence and clinical consequences of abnormal radiological and clinical findings during routinely performed 6-week outpatient visits in patients treated conservatively for multiple (3 or more) rib fractures. Methods: A retrospective analysis was conducted among patients with multiple rib fractures treated conservatively between 2018 and 2021 (Opvent database). The primary outcome was the incidence of abnormalities on chest X-ray (CXR) and their clinical consequences, which were categorized as requiring intervention or additional clinical/radiological examination. The secondary focus was the incidence of deviation from standard treatment in response to the findings (clinical or radiological) at the routine 6-week outpatient visit. Results: In total, 364 patients were included, of whom 246 had a 6-week visit with CXR. The median age was 57 years (interquartile range, 46-70 years) and the median Injury Severity Score was 17 (interquartile range, 13-22). Forty-six abnormalities (18.7%) were found on CXR. These abnormalities resulted in additional outpatient visits in 4 patients (1.5%) and in chest drain insertion in 2 (0.8%). Only 2 patients (0.8%) with an abnormality on CXR presented without symptoms. None of the 118 patients who had visits without CXR experienced problems. Conclusion: Routine 6-week outpatient visits for patients with conservatively treated multiple rib fractures infrequently revealed abnormalities requiring treatment modifications. It may be questioned whether the 6-week outpatient visit is even necessary. Instead, a more targeted approach could be adopted, providing follow-up to high-risk or high-demand patients only, or offering guidance on recognizing warning signs and providing aftercare through a smartphone application.

Long-term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre.

INTRODUCTION: Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines. METHODS: All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained. RESULTS: In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%. CONCLUSION: Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.

Selection Bias in Strong Coupling Experiments.

The strong coupling of light and molecules offers a potential new pathway to modify the properties of photonic modes and molecules. There are many reasons to be optimistic about the prospects of strong coupling; however, progress in this field is currently hindered by challenges in reproducibility, problems associated with differentiating between strong coupling and other effects, and the lack of a clear theoretical model to describe the reported effects. Concerning the question of differentiating between strong coupling and other possible mechanisms when examining experimental data, here, we show how cognitive bias can lead us to place undue emphasis on a given interpretation of unsystematic experimental data. We hope that this Viewpoint will, where appropriate, help readers to plan strong coupling experiments more carefully and evaluate the significance of the data obtained from them.

In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis.

BACKGROUND: In 2017, the US Food and Drug Administration initiated expansion of drug labels for the treatment of cystic fibrosis (CF) to include CF transmembrane conductance regulator (CFTR) gene variants based on in vitro functional studies. This study aims to identify CFTR variants that result in increased chloride (Cl-) transport function by the CFTR protein after treatment with the CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). These data may benefit people with CF (pwCF) who are not currently eligible for modulator therapies. METHODS: Plasmid DNA encoding 655 CFTR variants and wild-type (WT) CFTR were transfected into Fisher Rat Thyroid cells that do not natively express CFTR. After 24 h of incubation with control or TEZ and ELX, and acute addition of IVA, CFTR function was assessed using the transepithelial current clamp conductance assay. Each variant's forskolin/cAMP-induced baseline Cl- transport activity, responsiveness to IVA alone, and responsiveness to the TEZ/ELX/IVA combination were measured in three different laboratories. Western blots were conducted to evaluate CFTR protein maturation and complement the functional data. RESULTS AND CONCLUSIONS: 253 variants not currently approved for CFTR modulator therapy showed low baseline activity (<10 % of normal CFTR Cl- transport activity). For 152 of these variants, treatment with ELX/TEZ/IVA improved the Cl- transport activity by ≥10 % of normal CFTR function, which is suggestive of clinical benefit. ELX/TEZ/IVA increased CFTR function by ≥10 percentage points for an additional 140 unapproved variants with ≥10 % but <50 % of normal CFTR function at baseline. These findings significantly expand the number of rare CFTR variants for which ELX/TEZ/IVA treatment should result in clinical benefit.

Non-Polaritonic Effects in Cavity-Modified Photochemistry.

Strong coupling of molecules to vacuum fields is widely reported to lead to modified chemical properties such as reaction rates. However, some recent attempts to reproduce infrared strong coupling results have not been successful, suggesting that factors other than strong coupling may sometimes be involved. In the first vacuum-modified chemistry experiment, changes to a molecular photoisomerization process in the ultraviolet-visible spectral range are attributed to strong coupling of the molecules to visible light. Here, this process is re-examined, finding significant variations in photoisomerization rates consistent with the original work. However, there is no evidence that these changes need to be attributed to strong coupling. Instead, it is suggested that the photoisomerization rates involved are most strongly influenced by the absorption of ultraviolet radiation in the cavity. These results indicate that care must be taken to rule out non-polaritonic effects before invoking strong coupling to explain any changes of properties arising in cavity-based experiments.

Red Blood Cell Fatty Acid Profiles Are Significantly Altered in South Australian Mild Cognitive Impairment and Alzheimer's Disease Cases Compared to Matched Controls.

Nutritional imbalances have been associated with a higher risk for cognitive impairment. This study determined the red blood cell (RBC) fatty acid profile of newly diagnosed mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients compared to age and gender-matched controls. There was a significant increase in palmitic acid (p < 0.00001) for both MCI and AD groups. Saturated fatty acids were significantly elevated in the MCI group, including stearic acid (p = 0.0001), arachidic acid (p = 0.003), behenic acid (p = 0.0002), tricosanoic acid (p = 0.007) and lignoceric acid (p = 0.001). n-6 polyunsaturated fatty acids (PUFAs) were significantly reduced in MCI, including linoleic acid (p = 0.001), γ-linolenic acid (p = 0.03), eicosatrienoic acid (p = 0.009) and arachidonic acid (p < 0.00004). The n-3 PUFAs, α-linolenic acid and docosahexaenoic acid, were both significantly reduced in MCI and AD (p = 0.0005 and p = 0.00003). A positive correlation was evident between the Mini-Mental State Examination score and nervonic acid in MCI (r = 0.54, p = 0.01) and a negative correlation with γ-linolenic acid in AD (r = -0.43, p = 0.05). Differences in fatty acid profiles may prove useful as potential biomarkers reflecting increased risk for dementia.

In situ generation of cold atmospheric plasma-activated mist and its biocidal activity against surrogate viruses for COVID-19.

AIMS: To provide an alternative to ultra violet light and vapourized hydrogen peroxide to enhance decontamination of surfaces as part of the response to the COVID-19 pandemic. METHODS AND RESULTS: We developed an indirect method for in situ delivery of cold plasma and evaluated the anti-viral activity of plasma-activated mist (PAM) using bacteriophages phi6, MS2, and phiX174, surrogates for SARS-CoV-2. Exposure to ambient air atmospheric pressure derived PAM caused a 1.71 log10 PFU ml-1 reduction in phi6 titer within 5 min and a 7.4 log10 PFU ml-1 reduction after 10 min when the the PAM source was at 5 and 10 cm. With MS2 and phiX174, a 3.1 and 1.26 log10 PFU ml-1 reduction was achieved, respectively, after 30 min. The rate of killing was increased with longer exposure times but decreased when the PAM source was further away. Trace amounts of reactive species, hydrogen peroxide and nitrite were produced in the PAM, and the anti-viral activity was probably attributable to these and their secondary reactive species. CONCLUSIONS: PAM exhibits virucidal activity against surrogate viruses for COVID-19, which is time and distance from the plasma source dependent.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

INTRODUCTION: The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. METHODS: At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. RESULTS: Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. CONCLUSION: The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Amentotaxus×hybridia (Taxaceae), a new natural Amentotaxus hybrid from southeast Yunnan province, China.

During floristic surveys of Taxaceae in Hekou County, Yunnan Province, China, a putative natural hybrid between A.yunnanensis H.L. Li and A.hekouensis L.M. Gao was collected. Morphological and molecular evidence confirms its status as a natural hybrid. Amentotaxus×hybridia L.M. Gao has linear or linear-lanceolate leaves 6-13 cm × 1.0-1.5 cm, white stomatal bands with 34-40 rows on abaxial side, 2.5-3.5 mm, slightly wider than leaf margins; 3-6 seeds borne at the base of the branchlet, peduncle 1.3-1.6 cm long with 3-4 rows of persistent basal bracts.

Oleic Acid Status Positively Correlates with the Soluble Receptor for Advanced Glycation End-Products (sRAGE) in Healthy Adults Who Are Homozygous for G Allele of RAGE G82S Polymorphism.

BACKGROUND: The soluble form of receptor for advanced glycation end products (sRAGE) have been implicated in the prevention of numerous pathologic states, and highlights as an attractive therapeutic target. Because diets rich in monounsaturated fatty acids (MUFA) reduce postprandial oxidative stress and inflammation that is related to better health during aging, we investigated the association between red blood cell (RBC) fatty acids with circulatory AGE biomarkers and further stratified this correlation based on GG and GA + AA genotype. METHODS: A total of 172 healthy participants (median age = 53.74 ± 0.61 years) were recruited for the study. RBC fatty acid was analysed using gas chromatography and sRAGE was measured using a commercial ELISA kit. RESULTS: The result showed a non-significant correlation between total MUFA with sRAGE however oleic acid (C18:1) exhibited a positive correlation (r = 0.178, p = 0.01) that remained statistically significant (ß = 0.178, p = 0.02) after a stepwise multivariate regression analysis after adjusting for age, BMI and gender. In a univariate analysis, a positive significant correlation between C18:1 and sRAGE in GG genotype (r = 0.169, p = 0.02) and a non-significant correlation with GA + AA genotype (r = 0.192, p = 0.21) was evident. When C18:1 was stratified, a significant difference was observed for oleic acid and G82S polymorphism: low C18:1/GA + AA versus high C18:1/GG (p = 0.015) and high C18:1/GA + AA versus high C18:1/GG (p = 0.02). CONCLUSION: Our study suggests that increased levels of C18:1 may be a potential therapeutic approach in increasing sRAGE in those with GG genotype and play a role in modulating AGE metabolism.

PSMA-PET-guided dose-escalated volumetric arc therapy for newly diagnosed lymph node-positive prostate cancer: 5 Year outcomes following the FROGG and EviQ node-positive guidelines.

INTRODUCTION: The Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology Genitourinary Group (FROGG) guidelines and online EviQ protocols incorporate prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) for newly diagnosed lymph node (LN) positive prostate cancer. We evaluated late toxicity and efficacy outcomes following the FROGG and EviQ approach. METHODS: Patients with LN-positive-only metastases on PSMA-PET imaging were offered curative therapy with 3 months neoadjuvant androgen deprivation therapy (ADT) followed by DE-IMRT and 3 years adjuvant ADT. IMRT was delivered via volumetric arc therapy (VMAT). We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45 Fx to elective pelvic nodes, contoured using the PIVOTAL guidelines. RESULTS: Forty-five patients were included. The median number of PET-positive nodes boosted was 2 (range 1-6) and median boost volume 1.16 cc (range 0.15-4.14). Seventeen (38%) patients had PET-positive nodes outside of PIVOTAL contouring guidelines. With 60 months median follow-up, disease-free, metastasis-free, prostate cancer-specific and overall survival were 88.1%, 95.3%, 100% and 91.5%. There were no in-field nodal failures. Late grade 1, 2 and 3 gastrointestinal toxicities occurred in 4%, 2% and 0% of patients, and genitourinary toxicity in 18%, 18% and 4%. Lower limb grade 2 lymphoedema occurred in three patients (7%). CONCLUSION: Outcomes following FROGG guidelines and EviQ are promising, with high long-term disease control and low toxicity. Contouring guidelines require modification due to the high rate of PET-positive nodes demonstrated beyond recommended coverage.

Low Magnesium in Conjunction with High Homocysteine and Less Sleep Accelerates Telomere Attrition in Healthy Elderly Australian.

The relationship between sleep and micronutrients, including magnesium, is implicated in its regulation. The effects of low magnesium and other micronutrients on sleep disruption and telomere loss are not well understood. The present study was carried out in 172 healthy elderly subjects from South Australia. Plasma micronutrients including magnesium were measured. Each participant provided information about their sleep hours (<7 h or ≥7 h). Lymphocyte telomere length (TL) was measured by real-time qPCR assay. Plasma magnesium level was significantly low in subjects who sleep less than 7 h (p = 0.0002). TL was significantly shorter in people who are low in magnesium and sleep less than 7 h (p = 0.01). Plasma homocysteine (Hcy) is negatively associated with magnesium (r = −0.299; p < 0.0001). There is a significant interaction effect of magnesium and Hcy on sleep duration (p = 0.04) and TL (p = 0.003). Our results suggest that inadequate magnesium levels have an adverse impact on sleep and telomere attrition rate in cognitively normal elderly people, and this may be exacerbated by low levels of vitamin B12 and folate that elevate Hcy concentration.

Origin of an Anticrossing between a Leaky Photonic Mode and an Epsilon-Near-Zero Point of Silver.

Strong light-matter coupling hybridizes light and matter to form states known as polaritons, which give rise to a characteristic anticrossing signature in dispersion plots. Here, we identify conditions under which an anticrossing can occur in the absence of strong coupling. We study planar silver/dielectric structures and find that, around the epsilon-near-zero point in silver, the impedance matching between the silver and dielectric layers gives rise to an anticrossing. Our work shows that care must be taken to ensure that anticrossing arising from impedance matching is not misattributed to strong coupling.

Osteolytic Lesion of the First Metatarsal After Catfish Spine Injury: A Case Report.

CASE: A 17-year-old adolescent boy complained of plantar pain at the first metatarsal 2 months after a catfish spine injury. Imaging was consistent with a retained foreign body, and surrounding osteolysis was concerning for osteomyelitis. He underwent surgical debridement and was found to have inflammation and necrosis, apparently caused by catfish spine venom. CONCLUSION: Although osteolytic lesions are commonly attributed to infection or tumor, in the situation of venomous injuries, osteolysis can be a sequela of the severe local inflammatory reaction due to the toxins. Debridement is vital to remove the offending agent and the local toxins from the venom.

Efficient generation of entangled multiphoton graph states from a single atom.

The central technological appeal of quantum science resides in exploiting quantum effects, such as entanglement, for a variety of applications, including computing, communication and sensing1. The overarching challenge in these fields is to address, control and protect systems of many qubits against decoherence2. Against this backdrop, optical photons, naturally robust and easy to manipulate, represent ideal qubit carriers. However, the most successful technique so far for creating photonic entanglement3 is inherently probabilistic and, therefore, subject to severe scalability limitations. Here we report the implementation of a deterministic protocol4-6 for the creation of photonic entanglement with a single memory atom in a cavity7. We interleave controlled single-photon emissions with tailored atomic qubit rotations to efficiently grow Greenberger-Horne-Zeilinger (GHZ) states8 of up to 14 photons and linear cluster states9 of up to 12 photons with a fidelity lower bounded by 76(6)% and 56(4)%, respectively. Thanks to a source-to-detection efficiency of 43.18(7)% per photon, we measure these large states about once every minute, which is orders of magnitude faster than in any previous experiment3,10-13. In the future, this rate could be increased even further, the scheme could be extended to two atoms in a cavity14,15 or several sources could be quantum mechanically coupled16, to generate higher-dimensional cluster states17. Overcoming the limitations encountered by probabilistic schemes for photonic entanglement generation, our results may offer a way towards scalable measurement-based quantum computation18,19 and communication20,21.

All-optical control of phase singularities using strong light-matter coupling.

Strong light-matter coupling occurs when the rate of energy exchange between an electromagnetic mode and a molecular ensemble exceeds competing dissipative processes. The study of strong coupling has been motivated by applications such as lasing and the modification of chemical processes. Here we show that strong coupling can be used to create phase singularities. Many nanophotonic structures have been designed to generate phase singularities for use in sensing and optoelectronics. We utilise the concept of cavity-free strong coupling, where electromagnetic modes sustained by a material are strong enough to strongly couple to the material's own molecular resonance, to create phase singularities in a simple thin film of organic molecules. We show that the use of photochromic molecules allows for all-optical control of phase singularities. Our results suggest what we believe to be both a new application for strong light-matter coupling and a new, simplified, more versatile means of manipulating phase singularities.