A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

Clinical thermography at extreme temperatures.

Every day, emergency departments and acute medical units all over the world receive and assess thousands of patients. Most are stable, but a few require immediate stabilization. To identify these, all patients are routinely triaged and have vital signs measured. Our group has shown that thermographic images of the face can be an alternative method for identifying patients at increased risk of 30-day mortality. In our previous studies, the thermographic images were taken after the patients had been inside for at least 30 minutes. However, to identify patients at risk, the images have to be available as quickly as triage, i.e. at the door when the patient arrives. Therefore, we have performed a small study, with the aim of illustrating the effect of such heat-gradients on thermal images of the face.

Meloidogyne aegracyperi n. sp. (Nematoda: Meloidogynidae), a root-knot nematode parasitizing yellow and purple nutsedge in New Mexico.

Meloidogyne aegracyperi n. sp. is described from roots of purple nutsedge in southern New Mexico, USA. Mature females are small (310-460 µm), pearly white, with their egg masses completely contained inside root galls. The neck is often at a 90 to 130° angle to the protruding posterior end with the perineal pattern. The distance of the dorsal esophageal gland orifice (DGO) to the base of the stylet is relatively long (4.0-6.1 µm), and the excretory pore is level with the base of the stylet. The anterior portion of the rounded lumen lining of the metacorpus contains 3 to 10 small vesicles. The perineal pattern has a rounded dorsal arch with a tail terminal area that is smooth or marked with rope-like striae. Only two males were found. The body twists 90° throughout its length. The DGO to the base of the stylet is long (3.0-3.3) µm. The cephalic framework of the second-stage juvenile is weak, and the stylet is short (10.1-11.8 µm). The DGO to the base of the stylet is long (3-5 µm). The tail is very long (64-89 µm) and the hyaline portion of the tail is very narrow, making the tail finely pointed. Eggs are typical for the genus and vary in length (85.2-99.8 µm) and width (37.1-48.1 µm), having a L/W ratio of (2.1-2.6). Maximum likelihood phylogenetic analyses of the different molecular loci (partial 18S rRNA, D2-D3 of 28S rRNA, internal transcribed spacer (ITS) rRNA, cytochrome oxidase subunit II (COII)-16S rRNA of mitochondrial DNA gene fragments and partial Hsp90 gene) placed this nematode on an independent branch in between M. graminicola and M. naasi and a cluster of species containing M. chitwoodi. M. fallax, and M. minor. Greenhouse tests showed that yellow and purple nutsedge were the best hosts, but perennial ryegrass, wheat, bentgrass, and barley were also hosts.

Low-temperature laser-stimulated controllable generation of micro-bubbles in a water suspension of absorptive colloid particles.

A method is described for the generation of micrometer-sized vapor-gas bubbles in a water suspension containing absorptive pigment nanoparticles. The diluted suspension (mean interparticle distance 20 µm) absorbs the continuous laser radiation (wavelength 808 nm), and each particle in the best illuminated volume (~10 × 10 × 200 µm3) serves as a bubble-nucleation center. The suspension heating is inessential (several degrees above the room temperature) and the bubbles are formed mainly of the air gases dissolved in water. The bubbles can stably exist within or near the illuminated area where their location is governed by the competition between thermal and optical forces and can be controlled via the laser beam parameters. The method enables controllable creation, support, prescribed transportation, and destruction of the bubbles. This can be useful in applications aimed at precise sorting, transportation, and delivery of species in nano- and micro-engineering as well as for biomedical studies.

Controllable generation and manipulation of micro-bubbles in water with absorptive colloid particles by CW laser radiation.

Micrometer-sized vapor-gas bubbles are formed due to local heating of a water suspension containing absorptive pigment particles of 100 nm diameter. The heating is performed by CW near-infrared (980 nm) laser radiation with controllable power, focused into a 100 µm spot within a 2 mm suspension layer. By changing the laser power, four regimes are realized: (1) bubble generation; (2) stable growth of the existing bubbles; (3) stationary existence of the bubbles and (4) the bubbles' shrinkage and collapse. This behavior is interpreted based on the temperature conditions. The generation and evolution of single bubbles and ensembles of bubbles with controllable sizes and numbers is demonstrated. The bubbles are grouped within the laser-illuminated region and form quasi-ordered structures. They can easily be moved and transported controlled by the focal spot. The results are useful for applications associated with the precise manipulation, sorting and specific delivery in nano- and micro-engineering problems.

Influence of evanescent wave on birefringent microplates.

Mechanical action caused by the optical forces connected with the canonical momentum density associated with the local wavevector or Belinfante's spin angular momentum is experimentally verified. The helicity-dependent and the helicity-independent forces determined by spin momenta of different nature open attractive prospects for the use of optical structures for manipulating minute quantities of matter of importance in nanophysics, nanooptics and nanotechnologies, precision chemistry and pharmacology and in numerous other areas. Investigations in this area reveal new, extraordinary manifestations of optical forces, including the helicity-independent force caused by the transverse helicity-independent spin or vertical spin of a diagonally polarized wave, which was not observed and exploited up to recently. The main finding of our study consists in a direct experimental demonstration of the physical existence and mechanical action of this recently discovered extraordinary transverse component of the spin here arising in an evanescent light wave due to the total internal reflection of a linearly polarized probing beam with azimuthal angle 45° at the interface between the birefringent plate and air, which is oriented perpendicularly to the wavevector of an evanescent wave and localized over the boundary of the transparent media with polarization-dependent refraction indices.

New Mexico and the southwestern US are affected by a unique population of tomato spotted wilt virus (TSWV) strains.

Tomato spotted wilt virus (TSWV) is an important pathogen of many ornamental, greenhouse and agronomic crops worldwide. TSWV also causes sporadic problems in a number of crops in New Mexico (NM). Nucleocapsid gene sequences obtained from six different crop species across the state over four different years were used to characterize the NM TSWV population. This analysis shows that NM is affected by a unique TSWV population that is part of larger independent population present in the southwestern US. This population likely arose due to geographic isolation and is related to other TSWV populations from the US, Spain, and Italy.

Photoactive High Explosives: Substituents Effects on Tetrazine Photochemistry and Photophysics.

High explosives that are photoactive, i.e., can be initiated with light, offer significant advantages in reduced potential for accidental electrical initiation. We examined a series of structurally related tetrazine based photoactive high explosive materials to detail their photochemical and photophysical properties. Using photobleaching infrared absorption, we determined quantum yields of photochemistry for nanosecond pulsed excitation at 355 and 532 nm. Changes in mass spectrometry during laser irradiation in vacuum measured the evolution of gaseous products. Fluorescence spectra, quantum yields, and lifetimes were measured to observe radiative channels of energy decay that compete with photochemistry. For the 6 materials studied, quantum yields of photochemistry ranged from <10(-5) to 0.03 and quantum yield of fluorescence ranged from <10(-3) to 0.33. In all cases, the photoexcitation nonradiatively relaxed primarily to heat, appropriate for supporting photothermal initiation processes. The photochemistry observed was dominated by ring scission of the tetrazine, but there was evidence of more extensive multistep reactions as well.

Measurement of small light absorption in microparticles by means of optically induced rotation.

The absorption parameters of micro-particles have been associated with the induced spin exerted upon the particle, when embedded in a circularly polarized coherent field. The induced rotational speed is theoretically analyzed, showing the influence of the beam parameters, the parameters of the particle and the tribological parameters of the surrounding fluid. The theoretical findings have been adequately confirmed in experiments.

Long-term outcome after spinal cord infarctions.

OBJECTIVES: To investigate long-term outcome in patients with spontaneous spinal cord infarctions and secondly to compare outcome with that of patients with cerebral infarction. MATERIAL AND METHODS: The study includes 30 patients with spinal cord infarction discharged between 1995 and 2010. Surviving patients were contacted by telephone and sent a questionnaire. Data on employment, function, depression, fatigue, pain, and quality of life were obtained and compared to similar data obtained from a group of patients with cerebral infarction. RESULTS: Seven patients with spinal cord infarction had died after a mean follow-up of 7.1 years. Mortality was associated with poor functioning in the acute phase. Thirteen of 20 responding patients were able to walk. Compared to patients with cerebral infarction, patients with spinal cord infarction had significantly lower mortality, poorer functioning, higher re-employment rate, and more pain. CONCLUSION: Many patients with spinal cord infarction experience significant improvement. Even though functional outcome is worse, the mortality rate is lower and the frequency of re-employment higher among patients with spinal cord infarction compared to patients with cerebral infarction.

Self-action of continuous laser radiation and Pearcey diffraction in a water suspension with light-absorbing particles.

Water suspension of light-absorbing nano-sized particles is an example of a medium in which non-linear effects are present at moderate light intensities favorable for optical treatment of organic and biological objects. We study experimentally the phenomena emerging in a thin layer of such a medium under the action of inhomogeneous light field formed due to the Pearcey diffraction pattern near a microlens focus. In this high-gradient field, the light energy absorbed by the particles induces inhomogeneous distribution of the medium refraction index, which results in observable self-diffraction of the incident light, here being strongly sensitive to the medium position with respect to the focus. This technique, based on the complex spatial structure of both the incident and the diffracted fields, can be employed for the detection and measurement of weak non-linearities.

Optical correlation algorithm for reconstructing phase skeleton of complex optical fields for solving the phase problem.

We propose an optical correlation algorithm illustrating a new general method for reconstructing the phase skeleton of complex optical fields from the measured two-dimensional intensity distribution. The core of the algorithm consists in locating the saddle points of the intensity distribution and connecting such points into nets by the lines of intensity gradient that are closely associated with the equi-phase lines of the field. This algorithm provides a new partial solution to the inverse problem in optics commonly referred to as the phase problem.

'This is silent murder' - are we medicalising human distress caused by the reality of life as an asylum seeker in the UK?

The number of displaced people, including asylum seekers and refugees, in the UK continues to rise. This article highlights findings from two participatory community listening exercises on the topic of health of displaced people.

Self-diffraction of continuous laser radiation in a disperse medium with absorbing particles.

We study the self-action of light in a water suspension of absorbing subwavelength particles. Due to efficient accumulation of the light energy, this medium shows distinct non-linear properties even at moderate radiation power. In particular, by means of interference of two obliquely incident beams, it is possible to create controllable phase and amplitude gratings whose contrast, spatial and temporal parameters depend on the beams' coherence and power as well as the interference geometry. The grating characteristics are investigated via the beams' self-diffraction. The main mechanism of the grating formation is shown to be thermal, which leads to the phase grating; a weak amplitude grating also emerges due to the particles' displacements caused by the light-induced gradient and photophoretic forces. These forces, together with the Brownian motion of the particles, are responsible for the grating dynamics and degradation. The results and approaches can be used for investigation of the thermal relaxation and kinetic processes in liquid suspensions.

A qualitative exploration of a financial inclusion service in an English foodbank.

AIMS: Foodbanks provide emergency food provision. This need can be triggered by a change in circumstance or a crisis. Failures in the social security safety net are the most significant driver for hunger in the UK. There is some evidence that an advisory service which runs alongside a foodbank is more effective in reducing emergency provision and the duration and severity of hunger. The 'Making a Difference' project at an English foodbank is a pilot scheme aiming to increase financial resilience in their service users. From summer 2022, they introduced new advice worker roles, in partnership with Shelter [Housing advice] and Citizen's Advice [General, debt and benefits advice], aiming to pre-empt the need for foodbank use, to triage the financial needs of service users and refer appropriately to reduce repeat visits to the foodbank. METHODS: This qualitative study involved in-depth interviews with four staff and four volunteers to evaluate barriers, facilitators and potential friction points in referrals and partnership working. FINDINGS: Our data were analysed thematically into four themes: Holistic needs assessment; Reaching seldom heard communities; Empowerment; The needs of staff and volunteers. Two case studies illustrate the complexity of people's needs. CONCLUSION: A financial inclusion service operating within foodbanks giving housing, debt and benefits advice shows some promise in reaching people in crisis at the point of need. Based within the heart of a community, it appears to meet the complex needs of very vulnerable people who may have found mainstream support services inaccessible. This asset-based approach with the foodbank as a trusted provider enabled joined up, compassionate, holistic, and person-centred advice quickly cutting across multiple agencies, reaching underserved and socially excluded clients. We suggest that supportive services are needed for volunteers and staff who are vulnerable to vicarious trauma from listening and supporting people in crisis.

Mantis Shrimp Locomotion: Coordination and Variation of Hybrid Metachronal Swimming.

Across countless marine invertebrates, coordination of closely spaced swimming appendages is key to producing diverse locomotory behaviors. Using a widespread mechanism termed hybrid metachronal propulsion, mantis shrimp swim by moving five paddle-like pleopods along their abdomen in a posterior to anterior sequence during the power stroke and a near-synchronous motion during the recovery stroke. Despite the ubiquity of this mechanism, it is not clear how hybrid metachronal swimmers coordinate and modify individual appendage movements to achieve a range of swimming capabilities. Using high-speed imaging, we measured pleopod kinematics of mantis shrimp (Neogonodactylus bredini), while they performed two swimming behaviors: burst swimming and taking off from the substrate. By tracking each of the five pleopods, we tested how stroke kinematics vary across swimming speeds and the two swimming behaviors. We found that mantis shrimp achieve faster swimming speeds through a combination of higher beat frequencies, smaller stroke durations, and partially via larger stroke angles. The five pleopods exhibit non-uniform kinematics that contribute to the coordination and forward propulsion of the whole system. Micro-hook structures (retinacula) connect each of the five pleopod pairs and differ in their attachment across pleopods-possibly contributing to passive kinematic control. We compare our findings in N. bredini to previous studies to identify commonalities across hybrid metachronal swimmers at high Reynolds numbers and centimeter scales. Through our large experimental dataset and by tracking each pleopod's movements, our study reveals key parameters by which mantis shrimp adjust and control their swimming, yielding diverse locomotor abilities.

Lest we forget. Illuminating lived experience of the Covid-19 pandemic and lockdown.

The COVID-19 pandemic and associated 'lockdowns' profoundly impacted people's lives in 2020-2021 and beyond. This study sought to understand unique person-centred insights into health and wellbeing during the restrictive measures in the United Kingdom and to enable us to remember and give testimony to these lived experiences. Using photo-methods, participants from a larger cohort study which tracked people's behaviours during the pandemic were invited to share photographs and short text to visually illustrate their ephemeral and unique COVID-19 experiences. In total 197 participants shared 398 photographs. Using a critical realist approach in our design and analysis, we sought to gain an alternative viewpoint on what 'lockdown' and the pandemic meant. Our major findings revealed starkly contrasting experiences illustrated in our two major themes. Firstly loss, including ambiguous losses and a sense of loss, loss of freedoms and death. Secondly, salutogenesis (what makes us well) whereby participants were able to draw on assets which helped to keep them well by maintaining social connection, 'making the best of it', reconnecting with nature and appreciating the outdoors, creativity for pleasure and faith. Our findings illuminate widely differing experiences and indicate the powerful effect of assets that were perceived by our participants to protect their wellbeing. Understanding differential vulnerability will be essential going forward to target resources appropriately to those who have the least control over their lives, those with the greatest vulnerabilities and least assets which in turn could support a self-perpetuating recovery.

We care but we're not carers: perceptions and experiences of social prescribing in a UK national community organisation.

AIMS: (1) To explore how social prescribing referrals impact experiences of existing members of a voluntary and community-based organisation and (2) to describe the processes and relationships associated with joining community and voluntary organisations. METHODS: Online survey and qualitative interviews with members of Men's Sheds, a global volunteer-led initiative to address loneliness and social isolation in men. 93 self-selecting Shed members (average age 67 years, 93% male) from across England and Scotland took part in the survey about demographics, joining the Shed, and free-text questions about experiences in the Shed. From the survey participants, 21 Shed members were purposively sampled and interviewed to explore the impact of social prescribing and referrals on the Sheds. RESULTS: Participating in the Men's Shed was often associated with a significant change in personal circumstances, and Sheds provided a unique social support space, particularly valuable for men. Key factors around experiences of social prescribing and referral mechanisms were identified. We developed three themes: the experience of joining a Shed, success factors and risks of social prescribing, and 'we care but we're not carers'. CONCLUSIONS: The results show that Men's Sheds are a caring organisation, but their members are not trained as professional carers, and men come to the Shed for their own personal reasons. They are concerned about the potential additional responsibilities associated with formal referrals. They encourage the development of relationships and local-level understanding of the essence of Sheds to enable social prescribing. As models of social prescribing grow nationally and internationally, collaboratively working with voluntary and community organisations to develop a mutually beneficial approach is essential for the effectiveness and sustainability of social prescribing in community health.

Avelumab first-line maintenance treatment for advanced urothelial carcinoma: review of evidence to guide clinical practice.

The JAVELIN Bladder 100 phase III trial led to the incorporation of avelumab first-line (1L) maintenance treatment into international guidelines as a standard of care for patients with advanced urothelial carcinoma (UC) without progression after 1L platinum-based chemotherapy. JAVELIN Bladder 100 showed that avelumab 1L maintenance significantly prolonged overall survival (OS) and progression-free survival in this population compared with a 'watch-and-wait' approach. The aim of this manuscript is to review clinical studies of avelumab 1L maintenance in patients with advanced UC, including long-term efficacy and safety data from JAVELIN Bladder 100, subgroup analyses in clinically relevant subpopulations, and 'real-world' data obtained outside of clinical trials, providing a comprehensive resource to support patient management. Extended follow-up from JAVELIN Bladder 100 has shown that avelumab provides a long-term efficacy benefit, with a median OS of 23.8 months measured from start of maintenance treatment, and 29.7 months measured from start of 1L chemotherapy. Longer OS was observed across subgroups, including patients who received 1L cisplatin + gemcitabine, patients who received four or six cycles of 1L chemotherapy, and patients with complete response, partial response, or stable disease as best response to 1L induction chemotherapy. No new safety signals were seen in patients who received ≥1 year of avelumab treatment, and toxicity was similar in those who had received cisplatin or carboplatin with gemcitabine. Other clinical datasets, including noninterventional studies conducted in Europe, USA, and Asia, have confirmed the efficacy of avelumab 1L maintenance. Potential subsequent treatment options after avelumab maintenance include antibody-drug conjugates (enfortumab vedotin or sacituzumab govitecan), erdafitinib in biomarker-selected patients, platinum rechallenge in suitable patients, nonplatinum chemotherapy, and clinical trial participation; however, evidence to determine optimal treatment sequences is needed. Ongoing trials of avelumab-based combination regimens as maintenance treatment have the potential to evolve the treatment landscape for patients with advanced UC.

Orbital rotation without orbital angular momentum: mechanical action of the spin part of the internal energy flow in light beams.

The internal energy flow in a light beam can be divided into the "orbital" and "spin" parts, associated with the spatial and polarization degrees of freedom of light. In contrast to the orbital one, experimental observation of the spin flow seems problematic because it is converted into an orbital flow upon tight focusing of the beam, usually applied for energy flow detection by means of the mechanical action upon probe particles. We propose a two-beam interference technique that results in an appreciable level of spin flow in moderately focused beams and detection of the orbital motion of probe particles within a field where the transverse energy circulation is associated exclusively with the spin flow. This result can be treated as the first demonstration of mechanical action of the spin flow of a light field.