Early aerial expedition photos reveal 85 years of glacier growth and stability in East Antarctica.

During the last few decades, several sectors in Antarctica have transitioned from glacial mass balance equilibrium to mass loss. In order to determine if recent trends exceed the scale of natural variability, long-term observations are vital. Here we explore the earliest, large-scale, aerial image archive of Antarctica to provide a unique record of 21 outlet glaciers along the coastline of East Antarctica since the 1930s. In Lützow-Holm Bay, our results reveal constant ice surface elevations since the 1930s, and indications of a weakening of local land-fast sea-ice conditions. Along the coastline of Kemp and Mac Robertson, and Ingrid Christensen Coast, we observe a long-term moderate thickening of the glaciers since 1937 and 1960 with periodic thinning and decadal variability. In all regions, the long-term changes in ice thickness correspond with the trends in snowfall since 1940. Our results demonstrate that the stability and growth in ice elevations observed in terrestrial basins over the past few decades are part of a trend spanning at least a century, and highlight the importance of understanding long-term changes when interpreting current dynamics.

The multidisciplinary team in diagnosing and treatment of patients with diabetes and comorbidities: A scoping review.

Background: Multidisciplinary Teams (MDTs) has been suggested as an intervention to overcome some of the complexities experienced by people with diabetes and comorbidities in terms of diagnosis and treatment. However, evidence concerning MDTs within the diabetes field remains sparse. Objective: This review aims to identify and map available evidence on key characteristics of MDTs in the context of diagnosis and treatment in people with diabetes and comorbidities. Methods: This review followed the PRISMA-ScR guidelines. Databases PubMed, EMBASE, and CINAHL were systematically searched for studies assessing any type of MDT within the context of diagnosis and treatment in adult people (≥ 18 years) with diabetes and comorbidities/complications. Data extraction included details on study characteristics, MDT interventions, digital health solutions, and key findings. Results: Overall, 19 studies were included. Generally, the MDTs were characterized by high heterogeneity. Four overall components characterized the MDTs: Both medical specialists and healthcare professionals (HCPs) of different team sizes were represented; interventions spanned elements of medication, assessment, nutrition, education, self-monitoring, and treatment adjustment; digital health solutions were integrated in 58% of the studies; MDTs were carried out in both primary and secondary healthcare settings with varying frequencies. Generally, the effectiveness of the MDTs was positive across different outcomes. Conclusions: MDTs are characterized by high diversity in their outline yet seem to be effective and cost-effective in the context of diagnosis and treatment of people with diabetes and comorbidities. Future research should investigate the cross-sectorial collaboration to reduce care fragmentation and enhance care coordination.

The Effectiveness of Telemedicine Solutions in Type 1 Diabetes Management: A Systematic Review and Meta-analysis.

BACKGROUND: Telemedicine holds a potential to strengthen self-management support outside health care settings in the everyday management of type 1 diabetes (T1D). However, existing effectiveness reviews are older or include a relatively narrow focus on specific definitions of telemedicine or included databases. OBJECTIVE: To conduct a systematic review of the effectiveness of telemedicine solutions versus any comparator on diabetes-related outcomes among people with T1D. METHODS: Studies including adults (≥18 years) with T1D published before October 14, 2020, were eligible. Primary outcome was glycated hemoglobin (HbA1c, %). The Cochrane Library, PubMed, EMBASE, and CINAHL were searched. Meta-analysis based on the mean difference in HbA1c% was used to pool effects. The Cochrane tool was applied to assess risk-of-bias, and the certainty of evidence was graded using the GRADE approach. RESULTS: A total of 22 studies were included (with 1615 participants). Treatment effect for HbA1c% favored telemedicine (mean difference of -0.26% [95% confidence interval:-0.37% to -0.15%]) with moderate effect certainty. Heterogeneity was moderate (I2 = 33.30%). Although not significant, secondary outcomes were all in favor of telemedicine except number of severe hypoglycemic events and diabetes knowledge, but the certainty of the evidence for those outcomes was all low or very low. DISCUSSION: Reducing average HbA1c% levels are important to combat the risk of diabetic complications and premature death. However, the evidence mostly consist of small studies with a relative short duration and the estimated pooled effect is smaller than could be expected from quality improvement strategies in general for diabetes management. PROSPERO NUMBER: CRD42020123565.

The Effectiveness of Telemedicine Solutions for the Management of Type 2 Diabetes: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D). METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of -0.415% (95% confidence interval [CI] = -0.482% to -0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine. CONCLUSIONS: In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.

Effectiveness of Telemedicine in Managing Diabetes in Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: Strict monitoring of blood glucose during pregnancy is essential for ensuring optimal maternal and neonatal outcomes. Telemedicine could be a promising solution for supporting diabetes management; however, an updated meta-analysis is warranted. This study assesses the effects of telemedicine solutions for managing gestational and pregestational diabetes. METHODS: PubMed, EMBASE, Cochrane Library Central Register of Controlled Trials, and CINAHL were searched up to October 14, 2020. All randomized trials assessing the effects of telemedicine in managing diabetes in pregnancy relative to any comparator without the use of telemedicine were included. The primary outcome was infant birth weight. A meta-analysis comparing the mean difference (MD) in birth weight across studies was applied, and subgroup and sensitivity analyses were performed. The revised Cochrane tool was applied to assess the risk of bias, and the certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: From a total of 18 studies, ten (totaling 899 participants) were used to calculate the effect on infant birth weight. The results nonsignificantly favored the control (MD of 19.34 g; [95% confidence interval, CI -47.8; 86.47]), with moderate effect certainty. Heterogeneity was moderate (I2 = 37.39%). Statistically significant secondary outcomes included differences in two-hour glucose tolerance postpartum (gestational diabetes; two studies: standardized mean difference 9.62 mg/dL [95% CI: 1.95; 17.28]) that favored the control (GRADE level, very low) and risk of shoulder dystocia (four studies: log odds -1.34 [95% CI: -2.61; -0.08]) that favored telemedicine (GRADE, low). CONCLUSIONS: No evidence was found to support telemedicine as an alternative to usual care when considering maternal and fetal outcomes. However, further research is needed, including economic evaluations.

Distal symmetrical polyneuropathy is present in all individuals with diabetes and foot ulcers - and does not associate with healing time.

We estimated the occurrence of diabetic neuropathy using six different diagnostic modalities in individuals with newly diagnosed diabetic foot ulcers (DFUs) and assessed the association with DFU healing time. All individuals with DFU had distal symmetrical polyneuropathy. Presence of neuropathy did not associate with ulcer healing time (p ≥ 0.12).

Flexor Tendon Tenotomy Treatment of the Diabetic Foot: A Multicenter Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to evaluate the effects of needle flexor tendon tenotomy treatment of the diabetic hammertoe deformity. RESEARCH DESIGN AND METHODS: A multicenter randomized controlled trial of individuals with diabetes and ulcers or impending ulcers associated with hammertoes was performed between 1 November 2019 and 31 March 2021. Participants were stratified by the presence of ulcers or impending ulcers. Participants were randomly assigned to tenotomy and standard nonsurgical treatment or to standard nonsurgical treatment alone. Primary outcomes were time to ulcer healing and progression from impending ulcer to active ulcer. RESULTS: Of 224 screened participants with diabetes, 95 (59.0% men) were included. The mean follow-up was 291 ± 70 days, 28 (29.5%) had type 1 diabetes, mean diabetes (presented with 25-75% quartile) duration was 20 (13-26) years, and mean age was 67.7 ± 9.8 years. Of the included participants, 16 had ulcers, of whom 8 were randomly assigned to intervention. Of the remaining 79 with impending ulcers, 39 were randomly assigned to intervention. For participants with ulcers, healing rates favored tenotomy (100% vs. 37.5%, P = 0.026) as did time to ulcer healing (P = 0.04). For those with impending ulcers, incidence of progression to an active ulcer was lower (1 vs. 7, P = 0.028) and the number of ulcer-free days higher (P = 0.043) in the tenotomy group. No serious adverse events were recorded. CONCLUSIONS: This randomized study showed that the simple procedure of needle flexor tendon tenotomy was effective and safe when treating and preventing ulcers associated with the diabetic hammertoe deformity.

The influence of exercise on clinical pain and pain mechanisms in patients with subacromial pain syndrome.

BACKGROUND: Few studies have investigated the underlying mechanisms for unilateral subacromial pain syndrome (SAPS). Therefore, this study examined (1) if 8-weeks of exercise could modulate clinical pain or temporal summation of pain (TSP), conditioned pain modulation (CPM), and exercise-induced hypoalgesia (EIH) and (2) if any of these parameters could predict the effect of 8-weeks of exercise in patients with unilateral SAPS. METHODS: Thirty-seven patients completed a progressive abduction exercise program every other day for 8-weeks. Worst shoulder pain in full abduction was rated on a numeric rating scale (NRS). Pain pressure thresholds (PPTs), TSP, CPM, EIH, Shoulder Pain and Disability Index (SPADI), Pain Catastrophizing Scale (PCS), PainDETECT questionnaire (PD-Q), Pain Self-Efficacy Questionnaire (PSE-Q) and Pittsburgh Sleep Quality Index (PSQI) were assessed before and after intervention. RESULTS: The intervention improved worst pain intensity (p < 0.001), increased the CPM (p < 0.001), improved the sleep scores (p < 0.005) and reduced the PainDETECT ratings (p < 0.001). No changes were observed in PPT, TSP, EIH, SPADI, PCS and PSE-Q (all p > 0.05). In a linear regression, the combination of all baseline parameters predicted 23.2% variance in absolute change in pain after 8 weeks. Applying backwards elimination to the linear regression yielded that baseline pain intensity combined with TSP predicted 33.8% variance. CONCLUSION: This explorative study suggested reduction in pain, improved sleep quality and increased CPM after 8-weeks of exercise. Furthermore, the results suggests that low pain intensity and high TSP scores (indicative for pain sensitisation) may predict a lack of pain improvement after exercise.

The analogue substitution model: Introducing competition in the absence of generic substitution in Danish hospitals.

Increasingly advanced medicines have created monopolies in treatment areas with no viable options for generic substitution due to patent protection. As health care systems are increasingly under pressure to deliver health care improvements, costs become prohibitive as budgets are under pressure. To create financial flexibility, Danish regional authorities have over the period from 2009 until today developed, implemented, and gradually increased the use of a new model for analogue medicine substitution. The model introduces competitive tenders among patented medicines by declaring these medicines therapeutically equivalent in the treatment of specific diseases and thereby creating new opportunities for reducing annual medicine expenses. The model is based on enhanced collaboration among the health technology assessment (HTA) body, the procurement body, and the hospital owner, and it effectively covers medicine expenditure and cost-effectiveness while ensuring standardized treatments across hospitals and regions. The model is internationally unique in integrating several healthcare stakeholders and balancing their respective agendas to generate optimized outcomes for the healthcare system as a whole. However, some challenges persist, as the HTA process is resource and time consuming. Future research can show whether there are other challenges connected with the model.

Novel topical allogeneic bone-marrow-derived mesenchymal stem cell treatment of hard-to-heal diabetic foot ulcers: a proof of concept study.

AIM: The aim of this study was to investigate safety of treating diabetic foot ulcers with a topically administered mesenchymal stem cell product. METHOD: Individuals with diabetes, peripheral neuropathy, toe blood pressure > 39 mmHg and non-infected foot ulcers with duration of four to fifty-two weeks were screened. Participants were treated with a one-time application of a topically applied allogeneic cellular product containing CD362 enriched mesenchymal stem cells suspended in a collagen solution. Participants were subsequently followed for seven months to gather information on adverse event and serious adverse events. RESULTS/DISCUSSION: A total of sixteen individuals were screened, of whom two were included. The included participants incurred a total of seven adverse events and one serious adverse event. Increased exudation from the treated diabetic foot ulcer was observed for both participants and a connection to investigational medicinal product was suspected. The increased exudation was resolved within one week after application of investigational medicinal product, without any further complications. The serious adverse event consisted of a hospital admission due to neurological symptoms, which were assumed to be caused by hypoglycemia, with no suspected correlation to the investigational medicinal product. None of the other observed adverse events were suspected to be associated with the investigational medicinal product. CONCLUSION: This study presents data from two individuals with a diabetic foot ulcer treated with a novel topical mesenchymal stem cell product. An adverse event observed for both participants was suspected to be associated to the investigational medicinal product, i.e., increased exudation, which was resolved within one week, did not lead to further complications and can easily be remedied by choosing bandages with higher absorption capacity or increasing frequency of bandage changes. This study lays the groundwork for further large scale randomized clinical studies. TRIAL REGISTRATION: EudraCT number 2015-005580-16. Registered 12/06-2018.

Improvement of Caciotta-like cheese nutritional value by means of enrichment with blackcurrant (Ribes nigrum) and Cornelian cherry (Cornus mas).

Introduction: In this study, we supplemented models of Caciotta-like cheese with blackcurrant (Ribes nigrum) and Cornelian cherry (Cornus mas), as they have a high content of polyphenols, known as phytochemicals associated with health benefits. We evaluated the microbial composition, organoleptic aspects, total phenolic content, and chemical composition of model cheeses enriched with blackcurrant and Cornelian cherry. Methods: Two different suppliers have been tested: a conventional and an organic one. Two different conditions of preparation (freeze-dried and not freeze-dried) were tested in two different amounts (0.3 and 0.6% dry weight w/v milk volume). Polyphenols were determined using Folin-Ciocalteu reaction and spectrometry; microbial community was determined with selective 24 media and plate counts; composition was determined using nuclear magnetic resonance spectrometry. Organoleptic tests with an untrained panel have been performed. Results: The enrichments with blackcurrant and Cornelian cherry increased the total polyphenol content in model cheeses, in particular, when blackcurrant and Cornelian cherry were from conventional farming. Blackcurrant-enriched cheeses showed higher counts of lactic acid bacteria, higher levels of organic acids, amino acids, gamma-aminobutyric acid, histamine, and lower amount of monosaccharides deriving from bacterial lactose fermentation in cheese, suggesting a positive effect of blackcurrant compounds on the growth and activity of lactic acid bacteria. The enrichments did not affect the acceptance of the cheese, neither by blackcurrant nor by Cornelian cherry incorporation, with the exception of the appearance. Discussion: Overall, we showed that cheeses enriched with blackcurrant or Cornelian cherry from conventional farming increased the bioactive potential of the dairy product without having an adverse effect on the microbial community, physiochemical properties, or organoleptic properties.

Patient-recorded benefit from nasal closure in a Danish cohort of patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Nasal closure, also known as the modified Young's procedure was introduced in Denmark in 2008, as a surgical solution to severe epistaxis in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of this study was to report the overall satisfaction of the procedure from a patient's point of view as well as the occurrence of complications. METHODS: All the HHT patients who underwent nasal closure from 2008 to 2018 were included in the study. The patients were evaluated for postoperative complications and subjective outcome using Glasgow Benefit Inventory (GBI). RESULTS: Ten patients were included in the study and were observed for a mean of 64 months. None of the patients was completely free of complications, and reversal was requested in a single case. Haemoglobin levels rose with an average of 2.8 g/dl. The average GBI score after surgery was 38.05. Nine of ten patients would recommend nasal closure to fellow HHT patients. CONCLUSION: Nasal closure is highly recommended among patients, but due to the rate of postoperative complications, the procedure should be reserved for a carefully selected group of HHT patients.

The effect of needle tenotomy on hammer, mallet and claw toe deformities in patients with diabetes, a retrospective study.

AIM: The aim of this study was to evaluate outcomes of needle tenotomies as a treatment option for hammer, mallet and claw toes in patients with diabetes. METHODS: This was a retrospective study where all patients receiving flexor tendon tenotomy by needle at our outpatient clinic were identified through the electronic patient record system. RESULTS: A total of 81 patients that had 106 tenotomy procedures performed were identified. The 81 included (68% male) had an average age of 65.4 years, and 27 (33%) had Type 1 diabetes. Of the 106 procedures 36 were performed due to an ulcer on the feet. Of the 36 treated ulcers, 34 (94%) healed in an average time of 28 days. Tenotomies performed to prevent impending ulcers from progressing to active ulcers, were performed 84 times in total. Of the 84 procedures 6 patients progressed to an active ulcer. No serious complications i.e. infections or amputations in relation to the procedure were registered. CONCLUSION: Needle flexor tenotomies are a relatively safe and effective treatment compared to tenotomies done by scalpel, both as treatment for ulcers and to prevent formation of new ulcers associated with hammer, mallet and claw toe deformities. As a side note, transfer lesions are avoidable if all toes on one or both feet are tenotomized in one procedure.

[Bilateral caput femoris epiphysiolysis after epileptic seizures].

This case rapport is about a 12-year-old boy with loss of gait function over seven months after epileptic seizures. X-ray confirmed bilateral slipped capital femoral epiphysis (SCFE) probably with traumatic origin caused by the seizures. SCFE is characterised by slip of the epiphysis in relation to the metaphysis of the femoral bone. Traumatic SCFE is painful, and if untreated it can cause severe deformities and caput necrosis. Surgical treatment is necessary, one option is in situ fixation, which was the treatment of the boy in this report. At six-week post-operative control some stand function was regained.

Community maturity to implement Health in All Policies.

OBJECTIVES: To provide a fundament for practical guidance on implementation of HiAP to Danish Municipalities HiAP. METHODS: This study is based on a descriptive case study design where a mixed method is used. A questionnaire survey with 64 respondents was conducted in the five political sectors of Esbjerg municipality and it was followed up by four semi-structured interviews with key respondents based on a Dutch prototype model from 2014; The Capability Maturity Model for HiAP. RESULTS: The Maturity Model was applied in Esbjerg Municipality and proved practical for the assessment of the growth process of HiAP. Esbjerg municipality is assessed to be at maturity level 2 in the implementation process of HiAP, where the approach is recognized and considered to tackle health inequalities. CONCLUSION: The Maturity Model for HiAP has proved suitable for assessing the implementation process of HiAP on a municipality level and establishes a fundament for practical guidance in the area.

The capacity to maintain ion and water homeostasis underlies interspecific variation in Drosophila cold tolerance.

Many insects, including Drosophila, succumb to the physiological effects of chilling at temperatures well above those causing freezing. Low temperature causes a loss of extracellular ion and water homeostasis in such insects, and chill injuries accumulate. Using an integrative and comparative approach, we examined the role of ion and water balance in insect chilling susceptibility/ tolerance. The Malpighian tubules (MT), of chill susceptible Drosophila species lost [Na(+)] and [K(+)] selectivity at low temperatures, which contributed to a loss of Na(+) and water balance and a deleterious increase in extracellular [K(+)]. By contrast, the tubules of chill tolerant Drosophila species maintained their MT ion selectivity, maintained stable extracellular ion concentrations, and thereby avoided injury. The most tolerant species were able to modulate ion balance while in a cold-induced coma and this ongoing physiological acclimation process allowed some individuals of the tolerant species to recover from chill coma during low temperature exposure. Accordingly, differences in the ability to maintain homeostatic control of water and ion balance at low temperature may explain large parts of the wide intra- and interspecific variation in insect chilling tolerance.

Muscle membrane potential and insect chill coma.

Chill-susceptible insects enter a reversible paralytic state, termed chill coma, at mild low temperatures. Chill coma is caused by neuromuscular impairment, allegedly triggered by cold-induced depolarization of muscle resting membrane potential (Vm). We used five Drosophila species that vary in cold tolerance (chill coma temperature spanning ∼11°C) and repeatedly measured muscle Vm during a downward temperature ramp (20 to -3°C). Cold-tolerant species were able to defend their Vm down to lower temperatures, which is not explained by species-specific differences in initial Vm at 20°C, but by cold-tolerant drosophilids defending Vm across a broad range of temperatures. We found support for a previously suggested 'critical threshold' of Vm, related to chill coma, in three of the five species. Interestingly, the cold-tolerant Drosophila species may enter coma as a result of processes unrelated to muscle depolarization as their Vm was not significantly depolarized at their chill coma temperatures.

Temperate Drosophila preserve cardiac function at low temperature.

Most insects are chill susceptible and will enter a coma if exposed to sufficiently low temperature. This chill coma has been associated with a failure of the neuromuscular system. Insect heart rate (HR) is determined by intrinsic regulation (muscle pacemaker) with extrinsic (nervous and humoral) input. By examining the continually active heart of five Drosophila species with markedly different cold tolerance, we investigated whether cardiac performance is related to the whole animal critical thermal minimum (CTmin). Further, to separate the effects of cold on extrinsic and intrinsic regulators of HR, we measured HR under similar conditions in decapitated flies as well as amputated abdomens of Drosophila montana. Cardiac performance was assessed from break points in HR-temperature relationship (Arrhenius break point, ABP) and from the HR cessation temperature. Among the five species, we found strong relationships for both the HR-ABP and HR cessation temperatures to whole animal CTmin, such that temperate Drosophila species maintained cardiac function at considerably lower temperatures than their tropical congeners. Hearts of amputated abdomens, with reduced extrinsic input, had a higher thermal sensitivity and a significantly lower break point temperature, suggesting that central neuronal input is important for stimulating HR at low temperatures.

[Teminal care in a nursing home]. / Terminalforlob pa plejehjem

This article focuses on patients with limited life expectancy who no longer benefit from preventive medication but not yet qualify for palliative care - a time frame often referred to as End-of-Life (EOL). The purpose of this article is to identify and assess international guidelines for prescribing in EOL. No relevant clinical trials were available, but we found advice mainly based on logic assumptions and thoughts. Optimal prescribing for EOL patients remains mostly unexplored. Our study revealed two pivotal questions: How do we identify EOL patients, and what specific drugs should be removed?

Sodium distribution predicts the chill tolerance of Drosophila melanogaster raised in different thermal conditions.

Many insects, including the model holometabolous insect Drosophila melanogaster, display remarkable plasticity in chill tolerance in response to the thermal environment experienced during development or as adults. At low temperatures, many insects lose the ability to regulate Na(+) balance, which is suggested to cause a secondary loss of hemolymph water to the tissues and gut lumen that concentrates the K(+) remaining in the hemolymph. The resultant increase in extracellular [K(+)] inhibits neuromuscular excitability and is proposed to cause cellular apoptosis and injury. The present study investigates whether and how variation in chill tolerance induced through developmental and adult cold acclimation is associated with changes in Na(+), water, and K(+) balance. Developmental and adult cold acclimation improved the chilling tolerance of D. melanogaster in an additive manner. In agreement with the proposed model, these effects were intimately related to differences in Na(+) distribution prior to cold exposure, such that chill-tolerant flies had low hemolymph [Na(+)], while intracellular [Na(+)] was similar among treatment groups. The low hemolymph Na(+) of cold-acclimated flies allowed them to maintain hemolymph volume, prevent hyperkalemia, and avoid injury following chronic cold exposure. These findings extend earlier observations of hemolymph volume disruption during cold exposure to the most ubiquitous model insect (D. melanogaster), highlight shared mechanisms of developmental and adult thermal plasticity and provide strong support for ionoregulatory failure as a central mechanism of insect chill susceptibility.